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Editor’s Choice Potential Solutions in Radiation Hormesis
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Abstract: This study summarizes up-to-date information about the biopositive effects of low radiation treatment (LRT), radiation hormesis, and our experimental devices. In addition, we present a favorable treatment result in a patient with advanced rectal carcinoma who received LRT at home using a radon gas aspirator. The patient was a 61-year-old man who underwent proctectomy in 2010. During the additional first-line chemotherapy, apparent increases in tumor makers identified multiple remote metastases in the lung, sacrum and liver. Sacrum pain limited his activity of daily living and impeded his coming to our facility for LRT. Then, we decided to provide him home LRT using a radon gas aspirator. He inhaled radon gas for 15 minutes at least 3 times a day at home, resulting in remarkably reduced tumor markers and sacrum pain relief. He could walk, keep sitting up without support and sleep in the spine position again after receiving home LRT. No influence of radon gas inhalation on the second-line chemotherapy was observed. The favorable effects of LRT lead us to believe that the newly-developed devices will provide the clinical significance on malignant diseases. To establish the LRT regimen, further clinical investigation and data accumulation are thus called for. Keywords: Alternative treatment, low radiation treatment, radon gas, malignant diseases.Download Full Article |
Editor’s Choice : The Many Aspects of Off-Label Prescribing in Oncology
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Abstract: Off-label prescribing is particularly common in oncology. While it brings abundant benefits to cancer treatment, decisions on off-label prescribing should be made with caution, due to insufficient supporting data, weak safety monitoring system, and increased health care burden. Currently, reimbursement decisions for off-label oncology are based on recommendations from four drug compendia, each of which combines data from clinical trials and/or observational studies and expert opinions. Further enhancements are expected in terms of transparency and consistency of compendia’s methods of data synthesis. While the existing FDA regulations prohibit direct-to-prescriber promotion, with the exception of publication on off-label drug use, considerable leeway may be given to late-stage cancer patients. Clinical Trials for oncology off-label indication should focus on late stage cancer patients beyond first-line therapy and patient sample should have equal representations from academic and community settings. Off-label oncology clinical trials should also provide full information on conflict of interest. Given the high stakes involved in oncology treatment, future policies should strike a balance between innovation and clinical, economic, and humanistic consequences. Keywords: Off-label drug use, cancer, health policy, FDA, healthcare reimbursement.Download Full Article |
Editor’s Choice : Dietary Ascorbic Acid-Mediated Augmentation of Antitumor Activity and Protection Against Toxicities Induced by Cis-Diamminedichloroplatinum-(II) in Dalton’s Lymphoma-Bearing Mice
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Abstract: Cis-Diamminedichloroplatinum-(II) (CDDP) commonly known as cisplatin is considered as a major anticancer drug against a broad spectrum of malignancies. This study evaluates the modulatory effect of dietary ascorbic acid (AA) on the therapeutic efficacy of CDDP against murine ascites Dalton’s lymphoma (DL) and some tissue toxicities in tumor-bearing mice. As compared to CDDP alone, the combination treatment with ascorbic acid (AA) plus CDDP showed better therapeutic efficacy against murine ascites Dalton’s lymphoma. DL cells treated with CDDP showed the appearance of apoptotic features involving fragmentation of nucleus into discrete masses and plasma membrane blebbing. As compared to CDDP alone, combination treatment caused an increase in the number of apoptotic DL cells. Reduced glutathione (GSH) level was noted to decrease in DL cells while it increased in kidney after combination treatment. Blood haemoglobin (Hb), red blood cells (RBCs) and white blood cells (eosinophils, basophils and lymphocytes) were also decreased after CDDP treatment while overall betterment in hematological parameters was noted after combination treatment. The analysis of renal function tests (RFT) and liver function tests (LFT) suggest an improvement against CDDP-induced liver and kidney toxicities after combination treatment. The decrease in GSH levels particularly in DL cells and an increase in kidney and liver after combination treatment may have a role in the antitumor activity and decrease in CDDP-induced toxicity in the tumor-bearing host. Improvement in the LFT, RFT and hematological toxicities after combination treatment may have a beneficial effect in the improved survival of tumor-bearing mice. Keywords: Ascorbic acid, Apoptosis, cis-Diamminedichloroplatinum-(II), Dalton’s lymphoma, Reduced glutathione, Hematotoxicity.Download Full Article |
Editor’s Choice : Cancer Stem Cells: A Review of the Literature and the Implications in Head and Neck Cancer
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Abstract: In the last few decades, stem cells have been the focus of researchers in an effort to understand the molecular pathways involved in tissue regeneration. By studying normal cell interactions, researchers have since identified cancer stem cells and demonstrated their role in tumorigenesis and metastasis. The authors aimed to review the major molecular pathways involved in tumorigenesis, the role of cancer stem cells, and emerging therapies that target these pathways in squamous cell carcinoma of the head and neck. Keywords: Stem cells, cancer stem cells, head and neck, squamous cell carcinoma, hypoxia inducible factor, curcumin, cisplatin.Download Full Article |
Editor’s Choice : TRAP1 is Involved in Cell Cycle Regulated by Retinoblastoma Susceptibility Gene (RB1) in Early Hypoxia and has Variable Expression Patterns in Human Tumors
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Abstract: Tumor necrosis factor receptor associated protein 1(TRAP1) is a member of the Hsp90 family that acts as a molecular chaperon to the tumor suppressor retinoblastoma susceptibility gene (RB1). We have previously demonstrated that TRAP1-positive cells contain a high level of cell proliferating genes, whilst TRAP1-negative cells contain a high level of genes involved in cell cycles and metastases. In this study, we performed a functional analysis of TRAP1 which focused on its regulation within a cell cycle in relation to RB1. Following a heat shock, TRAP1 translocates to the nucleus and chaperonsRB1. When TRAP1 is silenced by siRNA, or prevented from entering the nucleus in hypoxic cells, formation of RB1/E2F1 complexes is impaired and cell cycle activity is promoted by deregulating the G1/S transition. Inhibition of the nuclear translocation of TRAP1 with geldanamycin abrogates its ability to maintain RB1 in a form that associates with E2F1. Restoration of TRAP1 expression reverses these effects. We analysed TRAP1/RB1 expression on 630 tumors by immunohistochemical staining and found TRAP1 lost in some types of cancer, such as non-small cell lung cancer and breast cancer, and the positive correlation of TRAP1 expression in nuclear and cytoplasm with RB1 was observed. Clinico-pathological data showed that breast carcinoma patients lacking nuclear TRAP1 have a shorter disease free survival. Our data suggests that nuclear translocation of TRAP1 is crucial for its function as a chaperon. The loss of TRAP1 expression in certain types of cancer may provide the growth advantage due to the lost control at cell cycle check point. Keywords: TRAP1, RB1, cell cycle, chaperon, hypoxia.Download Full Article |