がんの科学と治療

Cancer remains one of the most challenging diseases to treat in this new millennium. In an attempt to increase tumor response rates and decrease patient toxicity to various chemotherapeutic agents, the efficacy of metformin as a chemosensitizer was investigated. Preclinical and clinical evidence supports the use of metformin as a cancer therapeutic particularly in the treatment of cancers known to be associated with hyperinsulinemia, such as those of the breast and colon, as metformin has the ability to lower circulating insulin levels. Moreover, metformin may exhibit direct inhibitory effects on cancer cells by regulating cellular metabolism thereby reducing proliferation and inducing apoptosis. A variety of solid tumor single-cell heterogenates were incubated with chemotherapeutic agents, plus/minus metformin, and analyzed for cell-death. A total of fourteen solid-tumors of various types were studied; ten of the fourteen tumors (71%) exhibited poor or modest sensitivity to the chemo agents tested, but when metformin was combined, a synergistic effect was observed resulting in high sensitivity (high cell kill); one of the fourteen tumors (7%) exhibited a marginal sensitivity to metformin employed as a single agent. Our findings indicate a potential role for metformin in oncology therapeutics as a powerful adjuvant to chemotherapy in a wide range of cancer types.The diversity of the tumor specimens studied further validates the necessity to conduct clinical studies on the efficacy of metformin in the oncology setting. The clinical safety, wellcharacterized pharmacodynamic profile, and low cost of metformin make it an ideal candidate for development as an effective adjuvant anticancer agent. Nonetheless, a randomized controlled clinical trial must be designed to further correlate and validate this preliminary pilot study and to fully appreciate the impact of metformin on cancer recurrence and survival.

The purpose of this study was to identify current pattern of publication of the most influential radiation oncology
research, and to compare these previous pattern. From several potential measures of impact and relevance of
research, we selected article citation rate because landmark or practice-changing research is likely to be cited
frequently. The citation database Scopus was used to identify the 100 most frequently cited articles published
between 2009 and 2011, and 1999-2001, respectively. Current top 100 articles achieved a median of 57 citations
(range 181-38). Top 100 articles from the time period 1999-2001 achieved a median of 208 citations (range 1149-
121). The number of authors per highly cited article has increased significantly. Recently, 58% of articles were
written by more than 10 authors (1999-2001: only 25%). Significantly, fewer articles were published by authors from
the US and/or Canada (53% versus 73%). Pure European contributions increased from 20% to 33%. The proportion
of publications related to breast, lung or lower gastrointestinal tract cancer increased, while that related to prostate
or gynecological cancer decreased significantly. Irrespective of time period, pattern of publication was dominated
by only two scientific journals: the Journal of Clinical Oncology and the International Journal of Radiation Oncology
Biology and Physics. Several newly launched journals have managed to attract highly cited articles. Fifteen of the
20 journals (75%) that featured top 100 articles from the time period 1999-2001 were no longer represented on
the recent top 100 list. Inspite of changing pattern of publication, relatively few well established journals dominate.

A 12-year-old spitz breed dog, with progressive neurologic symptoms including seizures, ataxia, mental
depression, walking aimlessly and head pressing was referred to Small Animal Hospital of Veterinary Medicine,
the University of Tehran. The dog was received Diazepam prior to examination and diagnosis, whereas it died
at first day eventually. In physical examination, there was a firm mass with irregular nodular surface, about 8
cm in diameter under the skin of mammary glands region. At necropsy, considerable abdominal ascites, several
masses with different sizes throughout liver lobes and on intestinal serosa were observed. According to histological
adjectives of biliary epithelium due to firm texture of the tumour masses and numerous mitotic figures the tumour
was confirmed as cholangiocarcinoma, and immuniohistochemical results for cytokeratin marker demonstrated
such diagnosis.

Photodynamic therapy (PDT) is a promising treatment option for cancer. It can be used for drug-resistant and
inoperable tumors. However, one of the unsolved problems in PDT is tumor recurrence. The aim of this study is to
suppress tumor regrowth by including angiogenesis inhibitors that target vascular endothelial growth factor (VEGF)
and epidermal growth factor receptor (EGFR) pathways, to the PDT protocol. Human bladder cancer (MGH cell
line) xenografts were induced in Balb/c nude mice. The animals treated with PDT received an intravenous injection
of hypericin followed by irradiation after 6 hours, with a broadband light source through a 560-640 NM bandpass
filter. A light dosage of 120 J/cm2 and 100 mW/cm2 was administered. Angiogenesis inhibitors, bevacizumab
and cetuximab were administered at a dose of 10 mg/kg. Treatment efficacy was assessed by monitoring the
tumor growth inhibition of xenograft tumors. Immunohistochemistry was performed to evaluate the expression
of VEGF and EGFR. Expression of the major proteins in the VEGF and EGFR pathways was investigated by
immunoblotting. One-way ANOVA with Bonferroni correction was performed to analyze the data. Tumors treated
with the combination of PDT and inhibitors exhibited significantly greater treatment response compared to control
and PDT groups. Downregulation of VEGF and EGFR observed in tumors treated with PDT + bevacizumab
and cetuximab respectively. Our results show that blocking VEGF or/and EGFR pathways along with PDT can
effectively suppress tumor growth.