Showing papers in "Oncology in 2008"

Understanding and treating triple-negative breast cancer

Abstract: Triple-negative breast cancer is a subtype of breast cancer that is clinically negative for expression of estrogen and progesterone receptors (ER/PR) and HER2 protein. It is characterized by its unique molecular profile, aggressive behavior, distinct patterns of metastasis, and lack of targeted therapies. Although not synonymous, the majority of triple-negative breast cancers carry the "basal-like" molecular profile on gene expression arrays. The majority of BRCA1-associated breast cancers are triple-negative and basal-like; the extent to which the BRCA1 pathway contributes to the behavior of sporadic basal-like breast cancers is an area of active research. Epidemiologic studies illustrate a high prevalence of triple-negative breast cancers among younger women and those of African descent. Increasing evidence suggests that the risk factor profile differs between this subtype and the more common luminal subtypes. Although sensitive to chemotherapy, early relapse is common and a predilection for visceral metastasis, including brain metastasis, is seen. Targeted agents, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and poly (ADP-ribose) polymerase (PARP) inhibitors, are currently in clinical trials and hold promise in the treatment of this aggressive disease.

Radiation-induced lung injury. Assessment, management, and prevention.

Abstract: Radiation therapy (RT) is an important treatment modality for multiple thoracic malignancies Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress Replacement of normal lung parenchyma by fibrosis is the culminating event Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea Fibrosis of the lung, which can also cause dyspnea, is the late complication Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT

Psychological and Social Aspects of Breast Cancer

Abstract: Breast cancer treatments today are likely to cause less physical deformity from surgery than a half-century ago, but are more complex and extend over a longer period of time. Women today are often well informed about the details of their cancer diagnosis and prognosis, and are increasingly involved in shared decision-making regarding treatment. Although serious depression is not seen in the majority of breast cancer patients and survivors, many will experience treatment-related distress, fear of recurrence, changes in body image and sexuality, as well as physical toxicities that result from adjuvant therapy. This paper discusses the importance of identifying the psychological and social concerns of breast cancer patients in the medical setting, and assisting them in obtaining appropriate psychosocial services.

Role of MIF in inflammation and tumorigenesis.

Abstract: MIF has been described as a protein that plays an essential role in both innate and acquired immunity. Previous studies have demonstrated that MIF activates lymphocytes, granulocytes and monocytes/macrophages. Furthermore, MIF can counteract the physiological function of steroids, thus playing a role in immune system regulation. Further evidence for a role of MIF in immunity was obtained in mouse models of autoimmune disorders, where the inhibition of MIF resulted in a more benign disease progression. This observation made MIF an attractive therapeutic target for the treatment of these disorders. Moreover, MIF expression was found to be upregulated in a variety of different tumor cells, a finding that further attracted interest. This review provides an overview of the involvement of MIF in both autoimmune disorders and tumorigenesis and summarizes the molecular action of MIF in this context.

Sonazoid-Enhanced Ultrasonography for Diagnosis of Hepatic Malignancies: Comparison with Contrast-Enhanced CT

Abstract: Objective: The purpose of this study was to assess the usefulness of Sonazoid-enhanced ultrasonography (US) in the diagnosis of hepatic malignancies in comparison with contrast-enha

CD147, MMP-1, MMP-2 and MMP-9 protein expression as significant prognostic factors in human prostate cancer.

Abstract: Aim: CD147 and MMPs have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD147, MMP-1, MMP-2 and MMP-9 expression in human prostate cancer (PCa) and to evaluate their involvement in the progression of PCa. Methods: CD147, MMP-1, MMP-2 and MMP-9 expression was assessed in paraffin-embedded specimens collected from 62 cases of PCa and 15 cases of benign prostatic hyperplasia (BPH) by immunohistochemistry. Spearman’s correlation was applied to determine possible relationships between CD147, MMP-1, MMP-2 and MMP-9 expression and PCa. The association of CD147 and MMP-2 protein expression with the clinicopathological characteristics and the prognosis of PCa was subsequently assessed. Results: CD147was expressed in 51/62 (82.3%) PCa patients and in 2/15 (13.3%) BPH cases. MMP-1, MMP-2 and MMP-9 expression was significantly higher in PCa tissue than in BPH tissue. Using Spearman analysis, a significant positive correlation between CD147 and MMP-1, MMP-2 and MMP-9 expression was found (p Conclusion: The results suggest that concurrent expression of CD147 and MMP may be an important characteristic of PCa which may help in the prediction of PCa progression.

Hepatocellular carcinoma 2009 and beyond: from the surveillance to molecular targeted therapy.

Abstract: Hepatocellular carcinoma (HCC) is a malignant tumor which is becoming more prevalent worldwide. Patients at high risk of developing HCC, namely hepatitis B- and C-related liver cirrhosis patients, sho

Aromatase inhibitor-associated musculoskeletal symptoms: etiology and strategies for management.

Abstract: In the United States, approximately 180,000 women are diagnosed with breast cancer annually.

Synergizing radiation therapy and immunotherapy for curing incurable cancers. Opportunities and challenges.

Abstract: The combination of radiation therapy and immunotherapy holds particular promise as a strategy for cancer therapeutics. Evidence suggests that immunotherapy is most beneficial alone when employed early in the disease process or in combination with standard therapies (eg, radiation) later in the disease process. Indeed, radiation may act synergistically with immunotherapy to enhance immune responses, inhibit immunosuppression, and/or alter the phenotype of tumor cells, thus rendering them more susceptible to immune-mediated killing. As monotherapies, both immunotherapy and radiation may be insufficient to eliminate tumor masses. However, following immunization with a cancer vaccine, the destruction of even a small percentage of tumor cells by radiation could result in crosspriming and presentation of tumor antigens to the immune system, thereby potentiating antitumor responses. Learning how to exploit radiation-induced changes to tumor-cell antigens, and how to induce effective immune responses to these cumulatively immunogenic stimuli, is an exciting frontier in cancer therapy research. This review examines mechanisms by which many forms of radiation therapy can induce or augment antitumor immune responses as well as preclinical systems demonstrating that immunotherapy can be effectively combined with radiation therapy. Finally, we review current clinical trials where standard-of-care radiation therapy is being combined with immunotherapy.

Management of small-cell lung cancer: incremental changes but hope for the future.

Abstract: Over 25,000 people are diagnosed with small-cell lung cancer (SCLC) in the United States annually. SCLC is a highly aggressive tumor with a propensity for early metastases and a high case-fatality rate. Systemic treatment with etoposide plus a platinum agent is recommended for all stages of this disease and has been a standard first-line therapy for SCLC since the 1980s. Three recently presented randomized clinical trials failed to show superiority of newer regimens over etoposide and cisplatin. Patients with limited-stage (LS) disease benefit from the addition of radiotherapy to systemic chemotherapy, a combination that affords high complete response rates and potential cures. Incremental improvements in radiotherapy delivery over the past decade include the use of accelerated hyperfractionated thoracic radiotherapy for LS disease. Prophylactic cranial irradiation, previously recommended for patients with LS disease, has recently been shown to benefit those with extensive-stage (ES) disease as well. Surgery, largely abandoned in the 1970s, is being reevaluated as primary local therapy in patients with very early-stage SCLC. Topotecan remains the only US Food and Drug Administration-approved therapy for recurrent disease. Amrubicin has demonstrated single-agent activity in multiple phase II trials in both chemotherapy-sensitive and -refractory relapse. The past 2 decades have been marked by an improved understanding of SCLC biology, and these discoveries are reflected in the number and diversity of novel therapies entering early-phase testing in this disease.

A Treatment Selection Protocol for Recurrent Ovarian Cancer Patients : The Role of FDG-PET/CT and Staging Laparoscopy

Abstract: Objective: To investigate the best diagnostic and staging strategy for recurrent ovarian cancer. Methods: The negative predictive value, specificity, positive pre

Validation of a new prognostic staging system for hepatocellular carcinoma: a comparison of the biomarker-combined Japan Integrated Staging Score, the conventional Japan Integrated Staging Score and the BALAD Score.

Abstract: Objectives: The conventional Japan Integrated Staging (c-JIS) score has been reported to effectively stratify patients with hepatocellular carcinoma (HCC). Recently, two new staging

Epidemiology of hepatocellular carcinoma in Japan and Korea

Abstract: The worldwide burden of liver cancer has been estimated at 671,000 new cases for the year 2005. Hepatocellular carcinoma (HCC) accounts for between 85 and 90% of primary liver cancer and is one of the

Silencing of polo-like kinase (Plk) 1 via siRNA causes inhibition of growth and induction of apoptosis in human esophageal cancer cells.

Abstract: Esophageal cancer ranks among one of the most frequent causes of cancer death in the world. Polo-like kinase 1 (Plk1) is overexpressed in human tumors and has prognostic value in many cancers including esophageal cancer, indicating its potential as a therapeutic target. In this study, we investigated the therapeutic potential of Plk1 in esophageal cancer using the technique of RNA silencing via small interfering RNA (siRNA). Synthetic siRNA duplexes against Plk1 were introduced into 4 esophageal cancer cell lines, which subsequently resulted in a significant inhibition in Plk1 expression in the cells. We found that the targeted depletion of Plk1 caused a dramatic mitotic catastrophe (mitotic cell cycle arrest as well as defects in several mitotic events such as incomplete separation of sister chromatids and failure of cytokinesis) followed by massive apoptotic cell death, and eventually resulted in a significant decrease in growth and viability of all 4 esophageal cancer cell lines studied. In addition, our results also indicated that the mitotic arrest induced by Plk1 depletion is mediated by the inactivation of the cdc2/cyclin B1 complex. Taken together, our study strongly suggests that Plk1 may serve as a potential therapeutic target in human esophageal cancer.

Promoter Hypermethylation in Tumour Suppressor Genes Shows Association with Stage, Grade and Invasiveness of Bladder Cancer

Abstract: Aims: Superficial bladder cancer is a highly recurrent disease, with progression to muscle invasiveness occurring in 15–30% of cases. Promoter hypermethylation in a panel of tumour

Infectious port complications are more frequent in younger patients with hematologic malignancies than in solid tumor patients.

Abstract: Background: We assessed longevity and complications of totally implantable venous access devices in oncology patients. Methods: 197 patients received a total of 2

Response Evaluation of Transcatheter Arterial Chemoembolization in Hepatocellular Carcinomas: The Usefulness of Sonazoid-Enhanced Harmonic Sonography

Abstract: Background: The purpose of this study was to investigate if Sonazoid-enhanced harmonic ultrasonography (US) could be used to evaluate the responses of hepatocellular carcinomas (HCC

Adult Burkitt lymphoma: advances in diagnosis and treatment.

Abstract: Burkitt lymphoma is a unique B-cell malignancy with a high proliferation rate and characteristic genetic changes involving the c-myc oncogene. Burkitt lymphoma is common in children but also occurs in adults, where distinction from diffuse large B-cell lymphoma may pose a problem. The development of brief, very intensive chemotherapy regimens has led to a very high cure rate in children with Burkitt lymphoma. The use of these regimens in adults, often in combination with the antibody rituximab (Rituxan), has also made the cure of a majority of adults possible. Burkitt lymphoma in adults cannot be treated effectively with the common regimens used for diffuse large B-cell lymphoma such as CHOP-R (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone, rituximab). Prompt diagnosis and initiation of appropriate therapy with attention to the possibility of tumor lysis syndrome are necessary for optimal results.

Chemokine receptor CCR7 expression correlates with lymph node metastasis in pancreatic cancer.

Abstract: Aims: The clinical significance of chemokine receptor CCR7 expression in pancreatic ductal cancer was investigated. Methods: Immunohistochemical staining of 89 pa

Magnetic Resonance Imaging of Hepatocellular Carcinoma

Abstract: In hepatocellular carcinomas (HCCs), T1 shortening occurs due to internal protein, fat, copper, iron, hypercellularity, or a combination thereof. T1-weighted magnetic resonance i

Synergistic antileukemic activity of carnosic acid-rich rosemary extract and the 19-nor Gemini vitamin D analogue in a mouse model of systemic acute myeloid leukemia.

Abstract: Objective: Differentiation therapy with the hormonal form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3), is a promising approach to treatment of acute myelo

Hodgkin lymphoma in older patients: an uncommon disease in need of study.

Abstract: Elderly Hodgkin lymphoma (HL), commonly defined as occuring in patients over 60 to 65 years of age, is an uncommon disease. In population-based studies, the proportion of HL patients over age 60 years has rangedfrom 15% to 30%. However, the proportion of patients over age 60 years in clinical trials has been considerably lower, typically constituting < 5% to 10% of participants. Elderly HL patients commonly present with mixed cellularity histology, B symptoms, advanced stage, and Epstein-Barr virus-positive disease. Progression-free and overall survival rates for elderly HL patients are disproportionately inferior to those of younger patients. Generally, treatment of elderly HL for all disease stages should be given with curative intent, but more effective, tolerable therapeutic regimens are needed. No standard treatment recommendations exist for elderly HL Bleomycin-containing regimens including ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) are associated with pulmonary toxicity, and intensive therapy such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], procarbazine [Matulane], prednisone) is poorly tolerated, whereas less-intensive regimens such as CVP/CEB (chlorambucil [Leukeran], vinblastine, procarbazine, prednisone, cyclophosphamide, etoposide, bleomycin) and ChlVPP (chlorambucil, vinblastine, procarbazine, prednisolone) appear to be less effective than anthracycline-based regimens. Recent data using CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in this population merit further investigation. In addition, further evaluation of the prognostic value of early PET in elderly HL is warranted. Continued multicenter collaborations with prospective clinical trials, including formal assessment of comorbidity and functional status, will be critical to the successful study of elderly HL.

Bevacizumab Improves the Overall and Progression-Free Survival of Patients with Metastatic Colorectal Cancer Treated with 5-Fluorouracil-Based Regimens Irrespective of Baseline Risk

Abstract: Background: Kohne et al. [Ann Oncol 2002;13:308–317] showed that four prognostic variables can be used to classify patients with metastatic colorectal cancer (CRC) treated with 5-fl

Preliminary Results of the Combination of Bevacizumab and Weekly Paclitaxel in Advanced Melanoma

Abstract: Background: Pretreated advanced melanoma is a poor prognosis scenario with few, if any, active therapeutic options. The antibody against vascular endothelial growth factor, bevacizu

Clinical Significance of Insulin-Like Growth Factor Type 1 Receptor and Epidermal Growth Factor Receptor in Patients with Advanced Gastric Cancer

Abstract: Objective: To better understand the clinical implications of insulin-like growth factor type 1 receptor (IGF-1R), epidermal growth factor receptor (EGFR) and HER2 expressions in gas

Identification of genes targeted by CpG island methylator phenotype in neuroblastomas, and their possible integrative involvement in poor prognosis.

Abstract: Background/Aims: CpG island (CGI) methylator phenotype (CIMP) is strongly associated with poor prognosis in neuroblastomas (NBLs; hazard ratios 7–22). Methylation of nonpromoter CGI

Phase II Study of a Combination of S-1 and Paclitaxel in Patients with Unresectable or Metastatic Gastric Cancer

Abstract: Objectives: A phase II study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to evaluate the efficacy and tolerability in unresectable or metastatic gastric cancer. Patients and Methods: Twenty-nine patients with unresectable and/or metastatic gastric cancer were enrolled in the study. Paclitaxel 50 mg/m2 was administered on days 1 and 8. S-1 was administered orally at 40 mg/m2 b.i.d. for 14 consecutive days, followed by a 1-week rest. The primary endpoint was the response rate. Secondary endpoints were safety and overall survival. Results: The overall response rate in 29 patients was 48.3%, differentiated 36.4% and undifferentiated 55.6%. The median survival time was 13.9 months. Grade 3 or higher toxicity was observed in neutropenia (3.4%), diarrhea (3.4%), bilirubin (3.4%) and neuropathy (3.4%). Conclusions: Combination chemotherapy of weekly paclitaxel and S-1 demonstrated tolerable toxicity and efficacy. This regimen will be one of the initial treatment options for unresectable or metastatic gastric cancer.

Role of AIB1 for tamoxifen resistance in estrogen receptor-positive breast cancer cells.

Abstract: Objectives: The p160 nuclear receptor coactivator, AIB1 (amplified in breast cancer 1), is frequently overexpressed in human breast cancer and has been shown to be associated with t

Adjuvant Chemotherapy for Stage II Colon Cancer

Abstract: The use of adjuvant chemotherapy following resection for all patients with stage III colon cancer is now part of the standard of care around the world. Recent trials have led to changes in the standard regimens, which now include the use of oxaliplatin (Eloxatin) for most patients with stage III colon cancer. The addition of oxaliplatin has resulted in a 23% reduction in the risk of recurrence compared with fluorouracil/leucovorin alone, with a small but statistically significant survival benefit. Unfortunately, no adequately powered trial has determined whether adjuvant chemotherapy is beneficial for stage II patients, and its use is much more controversial. Most investigators agree that adjuvant chemotherapy has some activity against stage II disease. However, its impact on progression-free and overall survival remains highly controversial. Despite the lack of data, there is growing acceptance of an informal classification system, which stratifies stage II patients by risk on the basis of clinical data, as a guide for deciding whether to use adjuvant therapy. The only phase III clinical trial for stage II patients currently ongoing in the United States uses molecular classification as the basis for patient randomization.

Stimulation of proliferation of U138-MG glioblastoma cells by gastrin-releasing peptide in combination with agents that enhance cAMP signaling.

Abstract: Increasing evidence indicates that gastrin-releasing peptide (GRP) acts as an autocrine growth factor for brain tumors. However, it remains unclear whether the cAMP/protein kinase A (PKA) signaling pathway plays a role in mediating the mitogenic effects of GRP. We show here that GRP combined with agents that stimulate the cAMP/PKA pathway promotes proliferation of human gliobastoma cells. Treatment with GRP combined with the adenylyl cyclase activator forskolin, the cAMP analog 8-Br-cAMP or the phosphodiesterase type IV inhibitor rolipram increased proliferation of U138-MG cells in vitro measured by MTT assay. None of the compounds had an effect when given alone. GRP receptor (GRPR) mRNA and protein expression in U138-MG cells was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The results suggest that GRP and the GRPR interact with the cAMP/PKA signaling pathway in stimulating cancer cell proliferation.