Antiangiogenic therapy can generate a "normalization window" for tumor vasculature. This normalization process prunes immature vessels and improves the integrity and function of the remaining vasculature by enhancing the perivascular cell and basement membrane coverage in tumor, therefor creates a window of opportunity for improved sensitivity to ionizing radiation and the delivery of chemotherapeutic drugs. It provides a rational basis for the combination therapy of traditional Chinese drugs with radiation and perhaps other forms of chemotherapy. Antiangiogenic therapy with the traditional Chinese drug interfering in the the mechanisms of the normalization window in humans maybe harness a new approach to improve the sensitivity of tumors to radio- and chemotherapy.
Angiogenesis Inhibitors ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Neoplasms ; blood supply ; drug therapy ; immunology ; Neovascularization, Pathologic ; drug therapy ; Phytotherapy ; methods ; Tumor Microenvironment

OBJECTIVETo study the effect of angiogenesis inhibitor Rg3 on the growth and metastasis of gastric cancer in SCID mice.

METHODSMetastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Rg3 was administered by gastric perfusion at doses of 0, 2.5, 5.0, 10.0 mg/kg every day for 6 weeks 1 week after tumor implantation. One week after last administration, the mice were killed and their tumor weight was measured and the presence of metastasis recorded. Intratumoral microvessel density was examined by immunohistochemical staining with anti-CD31 monoclonal antibody.

RESULTSCompared to the untreated controls, the growth of the orthotopically implanted tumor was significantly reduced in weight in mice treated with Rg3 with an inhibition rate of 52.3%, 63.3% and 71.6% at doses of 2.5, 5.0, 10.0 mg/kg, respectively. Tumor metastasis to the liver and peritoneum was also significantly inhibited in a dose-dependent manner. Decreased intratumoral microvessel density was noted in the treated mice.

CONCLUSIONAngiogenesis inhibitor Rg3 has strong inhibitory effect on tumor growth and metastasis of human gastric cancer in SCID mice.

Angiogenesis Inhibitors ; therapeutic use ; Animals ; Antineoplastic Agents ; therapeutic use ; Female ; Ginsenosides ; therapeutic use ; Humans ; Mice ; Mice, SCID ; Neoplasm Metastasis ; Stomach Neoplasms ; blood supply ; drug therapy ; pathology

Accumulative evidences have underpinned the nature candidates from Chinese medicine (CM), particularly CM served as blood activating and stasis resolving (BASR, Huoxue Huayu in Chinese) by targeting tumor-associated angiogenesis. However, recent experiment research on the therapeutic angiogenesis by BASR-CM attracts wide attention and discussion. This opinion review focused on the underlying link between two indications and anticipated that (1) BASR-CM might emphasize on a balanced multi-cytokines network interaction; (2) BASR-CM might address on the nature of diseases prior to differently affecting physiological and pathological angiogenesis; (3) BASR-CM might mainly act on perivascular cells, either promotes arteriogenesis by increasing arteriogenic factors in ischemic diseases, or simultaneously keep a quiescent vasculature to impede angiogenesis in tumor context.
Angiogenesis Inhibitors ; chemistry ; therapeutic use ; Animals ; Antineoplastic Agents ; therapeutic use ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Models, Biological ; Neovascularization, Pathologic ; blood ; drug therapy

Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities. New molecular markers have emerged as potential diagnostic and prognostic indicators; these were summarized in Part I of this review in the Asian Journal of Andrology. A number of molecular markers are now being used to enhance PCa imaging and staging. However, management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed. Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation. Additionally, markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development. This review summarizes the current advances regarding the roles of these markers in the management of PCa.
Antineoplastic Agents ; therapeutic use ; Biomarkers, Tumor ; genetics ; metabolism ; Cancer Vaccines ; therapeutic use ; Genetic Therapy ; Humans ; Immunologic Factors ; therapeutic use ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; metabolism ; therapy

Tumor has long been a hard-nut problem in the world medical field. The effect of the conventional drugs is very limited because of the intervention of multiple micro-environmental factors during the occurrence and progression of tumors. With the characteristics of high efficiency, low toxicity and multi-targets synergistic effect, the long-circulating tumor targeted compound preparations show its unique advantages in improving tumor microenvironment and enhancing the therapeutic effect of treatment, thus it has gradually become a hotspot of studies both at home and abroad. Through consulting a great number of professional literatures at home and abroad in recent years, the authors summarized the current studies in vitro and in vive on long-circulating tumor targeted compound preparations in different carriers, in the expectation of providing new ideas and methods for the development of long-circulating tumor targeted compound preparations.
Animals ; Antineoplastic Agents ; blood ; chemistry ; therapeutic use ; Drug Compounding ; methods ; Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; blood ; drug therapy

The study was aimed to investigate the clinical efficacy and adverse reactions of different thalidomide regimens in the treatment of multiple myeloma (MM), and to explore the relationship between efficacy of thalidomide and serum level of TNF-alpha in MM patients. The 85 patients with MM were divided into 5 groups according to different combinations of thalidomide. These 5 groups were following: group with the high dose (HD-T), group with thalidomide+VAD chemotherapy (T-VAD), group with thalidomide+MP chemotherapy (T-MP), group with thalidomide plus dexamethasone (TD), and group with low dose of thalidomide (LD-T). Except 5 groups mentioned above, the group with conventional VAD chemotherapy was served as the control. Clinical effects, adverse reactions, treatment-related mortality were observed. At the same time, serum levels of TNF-alpha in 30 cases of MM treated with thalidomide (15 cases effective and 15 cases ineffective) before and after treatment were detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) and were compared with the clinical efficacy. The results showed that the efficient rate of HD-T, T-VAD, T-MP, TD, LD-T groups were 25.0%, 80.0%, 71.4%, 33.3%, 27.3% respectively; the efficacy of T-VAD, T-MP groups were significantly higher (p<0.05) than that of other groups and conventional VAD chemotherapy group. The incidence of significant adverse reactions (peripheral neuropathy, fatigue, abdominal distension and constipation, rash, edema, leukocyte and platelet decrease) in 5 groups were 75.0%, 30.0%, 28.6%, 14.3%, 9.1% respectively, no IV grade toxicity and deep vein thrombosis were found. The treatment-related mortality was 0%. At the same time, it was found that the serum levels of TNF-alpha in ineffective group treated with thalidomide were 44.7+/-5.7 pg/ml and 46.3+/-4.0 pg/ml before and after thalidomide treatment, and there was no significant difference (p>0.05). The serum levels of TNF-alpha (27.3+/-6.4) pg/ml in the effective group after treatment was significantly lower than that before treatment (49.2+/-7.3) pg/ml (p<0.05). It is concluded that compared with conventional chemotherapy, thalidomide is a effective drug for treating MM patients. Thalidomide in combination with chemotherapy (T-VAD, T-MP) may be one better therapeutic regimen with high efficiency and milder adverse reactions. Serum level of TNF-alpha is an indicator for finding effects of thalidomide, and plays a role in the pathogenesis of MM.
Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; blood ; drug therapy ; Thalidomide ; administration & dosage ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo analyze the clinical efficacy of imatinib mesylate (IM) for Ph-positive or BCR-ABL positive chronic myeloid leukemia (CML) to couple the trough plasma concentrations (C mins) of IM with clinical responses and adverse events (AEs).

METHODSOne hundred and one CML patients received IM therapy, and Cmins of IM were determined in 30 patients.

RESULTS(1) Cumulative complete hematological response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and negative BCR/ABL fusion gene rates were 96.6%, 86.5%, 77.5% and 47.2%, respectively, in CML-CP patients. In accelerated and blastic phases (AP and BC) patients, CHR, MCyR, CCyR and negative BCR-ABL fusion gene rates were 58.3%, 25.0%, 25.0%, 8.3%, respectively. (2) Mean Cmins of IM was significantly higher in the CCyR at 1 year [(1472 +/- 482) microg/L] group than in the non-CCyR at 1 years group [(1067 +/- 373) microg/L] (P < 0.05), and higher in the MMR at 1 year group than in the non-MMR at 1 years group [(1624 +/- 468) microg/L vs (1137 +/- 404) microg/L, P < 0.05].

CONCLUSIONIM significantly improves cytogenetic and molecular response, event-free survival, and overall survival for patients with Ph-positive CML. The Cmins of IM exerts a significant impact on clinical response (CCyR and MMR at 1 year).

Adolescent ; Adult ; Aged ; Antineoplastic Agents ; blood ; therapeutic use ; Benzamides ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult

BACKGROUNDCancer of the esophagus and gastroesophageal junction remains a virulent malignancy with poor prognosis. Rapid progresses were made in chemotherapeutic agents and the development of molecular markers allowed better identification of candidates for targeted therapy. This study aimed to identify the candidate peptides used for anti-angiogenic therapy of esophageal cancer by in vivo screening C7C peptide library for peptides binding specifically to blood vessels of human esophageal cancer.

METHODSThe phage displayed C7C peptide library was injected intravenously into mice bearing human esophageal tumor xenografts under renal capsule. After 5 rounds of screening, 13 clones were picked up individually and sequenced. During each round of screening, titers of phage recovery were calculated from tumor xenograft and control tissues. Homing of these 9 peptides to tumor vessel was detected by calculating phage titers in the tumor xenograft and control tissues (lung and spleen) after each phage was injected into mice model, and compared with the distribution of phage M13 and VIII-related antigen in tumor xenograft by immunohistochemical staining. Comparisons among groups of data were made using one-way analysis of variance (ANOVA), followed by the Bonferroni multiple comparisons test.

RESULTSThe number of phage recovered from tumor tissue of each round increased gradually in tumor group while decreased in control groups (P < 0.01 in tumor and spleen, P < 0.05 in lung). Immunohistochemical staining showed similar staining pattern with M13 antibody or VIII-related antigen antibody, suggesting that phages displaying the selected peptides could home to blood vessel of human esophageal cancer. According to their DNA, 9 corresponding peptide sequences were deduced. And the homing ability to blood vessel of phages displaying the selected peptides was confirmed by comparing with their recovery in tumor and control tissues. Two motifs, YSXNXW and PXNXXN, were also obtained by analyzing the homology of these peptide sequences. The staining distribution of phage with the sequence of PNPNNST was similar to that of the blood vessel marker factor VIII-related antigen staining. After sequencing, each phage with the selected peptide of PNPNNST with 1.0 × 10(11) pfu/ml was injected intravenously into mice. The homing ability to tumor vessel of these 9 kinds of peptides in the xenograft was higher than control tissues (lung and spleen).

CONCLUSIONNine peptides obtained from in vivo screening homed to the blood vessel of human esophageal cancer, and the two motifs of YSXNXW and PXNXXN are the possible biochemical recognition units binding to vascular endothelial cells of esophageal cancer.

Animals ; Antineoplastic Agents ; therapeutic use ; Endothelial Cells ; drug effects ; Esophageal Neoplasms ; blood supply ; drug therapy ; metabolism ; Humans ; Immunohistochemistry ; Mice ; Mice, Inbred BALB C ; Peptide Library ; Peptides ; therapeutic use

We aimed to evaluate the current nationwide trend, efficacy, safety, and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea. A total of 292 men with any biopsy-proven PCa (TanyNanyMany) from 12 institutions in Korea were included in this multi-institutional, observational study of prospectively collected data. All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs. Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl^-1) at 4-week visit and (2) breakthrough (serum testosterone >50 ng dl^-1 after castration). Safety assessments included routine examinations for potential adverse events, laboratory tests, blood pressure, body weight, and bone mineral density (BMD, at baseline and at the last follow-up visit). QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26). The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0%), and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0% for combination and 58.0% for monotherapy). The castration and breakthrough rates were 78.4% and 6.6%, respectively. The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment. In addition, the mean BMD T-score was significantly lower at the last follow-up (mean: -1.950) compared to baseline (mean: -0.195). The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]: 12.2) to 78.3 (s.d.: 8.1), with significant deterioration only in the urinary domain (mean: 23.5 at baseline and 21.9 at the 4-week visit). These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.
Aged ; Androgen Antagonists/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Cholesterol/blood* ; Drug Therapy, Combination ; Humans ; Leuprolide/therapeutic use* ; Male ; Middle Aged ; Prostatic Neoplasms/pathology* ; Quality of Life ; Receptors, LHRH/agonists* ; Republic of Korea ; Testosterone/blood* ; Treatment Outcome ; Triglycerides/blood*

PURPOSE: To evaluate the efficacy of carcinoembryonic antigen (CEA) measurement for monitoring tumor progression during palliative chemotherapy in metastatic colorectal cancer. MATERIALS AND METHODS: Forty-eight patients with initially unresectable metastatic colorectal cancer (n=26, 54.2%) or recurrent unresectable metastatic colorectal cancer (n=22, 45.8%) received FOLFOX-4 chemotherapy for palliation. Serum CEA levels and carbohydrate antigen 19-9 levels were measured and computed tomography (CT) studies were performed prior to chemotherapy and after 3 cycles of chemotherapy. From the CT images, tumor responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria and categorized as complete response, partial response, stable disease, and progressive disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of tumor marker assessments for determining tumor response were calculated. RESULTS: The sensitivity, specificity and diagnostic accuracy of CEA assessment for prediction of disease progression were 50%, 77% and 69%, respectively. When the patients were dichotomized according to baseline CEA level, the initially elevated CEA group showed higher sensitivity and higher diagnostic accuracy compared to the initially normal CEA group (sensitivity=67% vs. 20%; diagnostic accuracy=71% vs. 62%). CONCLUSION: CEA assessment could be useful for monitoring tumor progression during palliative chemotherapy in only patients with initially elevated CEA level.
Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CA-19-9 Antigen/metabolism ; Carcinoembryonic Antigen/*blood ; Colorectal Neoplasms/drug therapy/*metabolism ; Disease Progression ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Male ; Middle Aged ; Organoplatinum Compounds/therapeutic use ; Palliative Care ; Predictive Value of Tests ; Recurrence ; Reproducibility of Results ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Tumor Markers, Biological/blood