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[18F]-Fluoro-deoxyglucose positron emission tomography / computer tomography (18F-FDG PET/CT) is able to detect and assess the abnormal metabolism, enabling visualization and quantification in vivo with integration into CT anatomic information. The clinical usefulness of FDG PET/CT in the management of patients with sarcomas has been assessed by numerous investigators. Sarcomas are solid malignant tumors with distinct clinical and pathological features. Effective management of patients with sarcoma requires accurate diagnosis and staging. The authors discuss the major indications of PET/CT on the basis of literature data for diagnosis, staging, guidance of biopsy and monitoring response to therapy in both primary bone and soft tissue tumors. The consistent use of PET molecular imaging methods is of high importance in characterizing and understanding sarcoma behavior in clinical practice.A 18F-fluorodezoxi-glükóz pozitronemissziós tomográfia/komputertomográfia (18F-FDG PET/CT) in vivo nem invazív módon detektálja és kvantifikálja az emberi testben zajló kóros glükózmetabolizmust a CT morfológiai adatokba vetítve. Az irodalomban számos munkacsoport foglalkozik a PET/CT-alkalmazások klinikai jelentõségével sarcomás betegekben. A sarcomák szolid malignus tumorok, eltérõ klinikai és patológiai jellemzõkkel, amelyeknek a pontos mérése és feltérképezése számos esetben nélkülözhetetlen a betegek optimális terápiás vezetésében. A szerzõk az eddigi tapasztalatok és az irodalmi adatok felhasználásával elemzik a 18F-FDG PET/CT-alkalmazások szerepét a primer csont- és lágyrészsarcomák diagnózisában, a stádiummeghatározásban, a biopsziavételi hely megfelelõ feltérképezésében, a terápiás válasz monitorozásában, a betegek utánkövetésében és a prognosztikában. A molekuláris PET-képalkotás alkalmazása a klinikai gyakorlatban kulcskérdés a sarcomák felismerésében és karakterizálásában.

Modern imaging techniques have an important role in the diagnostic procedures of malignancies, and assessing response to therapy. The 18F-FDG PET/CT revolutionized the evaluation of colorectal cancer in terms of preoperative staging and monitoring of recurrence. Conventional imaging techniques have limitations in early assessment of response to therapy. 18F-FDG PET has been shown to allow earlier treatment monitoring, because the metabolic change appears before any anatomic change occurs. The Response Evaluation Criteria in Solid Tumours (RECIST) are widely applied, but they have some limitations. There are new international guidelines for treatment response assessment using PET/CT in solid tumours. The authors review indications and the role of hybrid PET/CT in colorectal cancer.A modern képalkotó vizsgálatoknak a daganatos betegségek diagnosztikájában és a kezelés hatékonyságának megítélésében fontos szerep jut. Colorectalis carcinomák esetén a 18F-FDG PET/CT vizsgálatot a műtét előtti stádiummeghatározásra és a kiújulás igazolására javasolják. A morfológiai képalkotó módszereknek korlátai vannak, elsősorban az új kemoterápiás kombinációban alkalmazott úgynevezett célzott terápiák hatásosságának korai megítélésében. Mivel a metabolikus változások megelőzik a tumor méretbeli változását, ezért ezen a területen a PET/CT vizsgálatok egyre nagyobb szerephez jutnak. Az eddig alkalmazott RECIST-kritériumok mellett a metabolikus válasz mérésére szolgáló kritériumrendszert is létrehoztak. A szerzők közleményükben az irodalmi adatok alapján a kombinált PET/CT technika javallatait és szerepét tekintik át vastag- és végbélrákok esetén. Orv. Hetil., 2013, 154, 1447–1453.

Disturbances of the carbohydrate metabolism are fairly common is patients with malignancy. On the other hand, diabetes appears to have an effect on the development and progression of various tumors. Malignant diseases and the therapies used in their treatment often have an impact on carbohydrate metabolism, while diabetes may hinder specific oncotherapy or influence oncological therapeutic decisions. Several complications of malignant diseases and some of the medications used in their treatment, such as steroids or parenteral nutrition, may raise blood glucose levels. The various obstacles of oral nutrition frequently seen in patients with malignancy can lead to hypoglycaemia in patients with diabetes. Our article endeavours to review the pathophysiological and clinical connection between diabetes and malignant diseases and the use of insulin, oral antidiabetic drugs and diet in patients with malignant disease.Daganatos betegekben gyakoriak a szénhidrátháztartás zavarai, és a diabetes mellitus hatással van egyes daganatok elõfordulására és progressziójára. A daganatos betegség maga és a specifikus onkoterápia is befolyásolhatja a szénhidrát-anyagcserét, de a diabetes is akadálya lehet a daganat eredményes kezelésének. Dolgozatunkban igyekszünk összefoglalni a két betegség közötti kórtani és klinikai összefüggéseket. Áttekintjük az onkoterápia hatásait a szénhidrát-anyagcserére és az antidiabetikus terápiák, az inzulinok, az orális antidiabetikumok és a diéta használatát daganatos betegekben.

In our retrospective study the pathological and clinical factors, influencing the survival of 65 renal clear cell carcinoma patients operated for bone metastasis between 1990 and 2008 were examined. Based on Kaplan-Meier curves age, gender, clinical symptoms, pathological fracture, progression to the soft tissues, localization and size of the metastasis, whether the occurrence of multiplex metastases is multiorganic or only located to the skeletal system and the stage and grade of primary renal cancer did not influence the survival. The survival significantly improved if the bone metastases were solitary, low Fuhrman grade, late onset; and radical surgery was performed. Based on Cox regression analysis, survival after bone surgery was influenced by the multiplicity and grade of metastasis and by the radicality of the surgery, whereas survival after nephrectomy was significantly influenced by onset time and grade of metastasis. When the solitary metastasis was radically removed, 75.0% of the patients survived the first, and 35.5% the fifth postoperative year. If the metastasis was multiple or the surgery was not radical, no patient survived the fifth year. This is the first report on the prognostic significance of the Fuhrman grade of bone metastasis of renal cell cancer. While the Fuhrman grade of the primary tumour did not influence the survival, the lower grade of metastasis was associated with a significant longer survival. Therefore in cases of solitary, operable, late onset metastases with low Fuhrman grade radical removal is recommended, since this way in 35.5% of cases 5 year survival can be expected.

The incidence of cholangiocarcinomas originating from intrahepatic and extrahepatic bile ducts, as well as of gallbladder carcinoma is increasing worldwide. The malignant transformation of biliary epithelia involves profound alterations of proteins in the intercellular junctions, among others zonula occludens-1 (ZO-1), occludin, and E-cadherin. Each plays important role in the maintenance of epithelial cell polarity and regulation of cell growth and differentiation. Our aim was to investigate ZO-1, occludin, and E-cadherin immunohistochemical reactions in tissue microarray blocks containing 57 normal and 62 neoplastic biliary tract samples. We demonstrated that the tight junction components ZO-1, occludin, and E-cadherin are downregulated in carcinomas arising from various compartments of the biliary tract (normal intrahepatic and extrahepatic bile ducts, gallbladder) as compared with their normal sites of origin. These results were confirmed by discriminant analysis yielding clear separation of the three normal sample groups from carcinomas in the corresponding locations.

Biliary tract cancers are relatively common malignant gastrointestinal tumors in the elderly. Claudins are integral components of tight junctions that play important roles in maintaining epithelial cell polarity, controlling paracellular diffusion, and regulating cell growth and differentiation. The expression profile of claudins has been extensively characterized, but few reports exist on their expression in the normal and neoplastic biliary tract. Our aim was therefore to study claudins by IHC reactions in normal and neoplastic biliary tract samples. We detected that claudin expressions differ in the normal sample groups: the normal gallbladder strongly expressed claudin-2, -3, -4, and -10, but only weak reactions were seen in normal intrahepatic bile ducts. Although each cancer type expressed several claudins with various intensities, only claudin-4 presented especially strong immunoreactions in extrahepatic bile duct cancers and gallbladder carcinomas, whereas claudin-1 and -10 presented in intrahepatic bile duct cancers. Comparing the normal and carcinoma groups, the most significant decrease was detected in the expression of claudin-10. In conclusion, the expression pattern of claudins is different in the various parts of the normal and neoplastic biliary tract; moreover, an unequivocal decrease was detected in the carcinomas compared with their corresponding normal samples. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 57:113–121, 2009)

Claudins (CLDN) are tight junction proteins which contribute to the paracellular transport and ionic permeability of various epithelia. In recent years they came into focus for their suggested role in carcinogenesis and possible role in cancer therapy. According to our previous studies, in breast tissue CLDN4 is also related to the level of cellular differentiation. Thirty-eight estrogen (ER) and progesterone receptor (PgR) negative, HER2/neu negative, but cytokeratin 5/6 positive basal-like—mainly grade 3—breast carcinomas were compared with twenty-one grade 1, twenty-five grade 2 and twenty grade 3 non-basal-like invasive breast carcinomas, in respect to their CLDN4 expression. The immunohistochemical reactions were evaluated both semiquantitatively and by morphometrical analysis. Statistically significant difference (p = 0.001) was observable regarding CLDN4 expression in the basal-like group as compared to grade 1 and 2 cancers. Further, CLDN4 expression was significantly higher (p = 0.017) in the basal-like compared with the non-basal-like grade 3 carcinomas. Our results suggest that basal-like carcinomas are a subset of breast cancer with high level of CLDN4 protein expression. The finding is in accordance with our former observation that CLDN4 is indeed related to cellular differentiation. This observation may be seen as a further proof that basal-like carcinomas represent a separable group amongst grade 3 breast carcinomas.

Background Colorectal Cancer (CRC) is the second most common cause of cancer death, with 40% of patients with this disease obtaining no benefit from current chemotherapy. Novel therapeutic strategies are needed to improve CRC patient response rates and survival. FLIP is an inhibitor of the extrinsic apoptotic pathway that binds to FADD at death-inducing signalling complexes (DISCs), such as those formed by the TNF-α-related apoptosis inducing ligand (TRAIL) receptors TRAIL-R1 and TRAIL-R2, thereby blocking homodimerization and activation of procaspase-8 and inhibiting apoptosis induction. We previously reported that FLIP blocks apoptosis induced by TRAIL and standard-of-care chemotherapeutics (5-Fluorouracil, oxaliplatin and SN38) in CRC models. Moreover, FLIP is frequently overexpressed in CRC and its overexpression correlates with poor prognosis. Subsequently, we have developed novel small molecule inhibitors that target FLIP's critical protein-protein interactions, preventing its interaction with FADD and therefore promoting activation of caspase-8 and apoptosis induction. Methods A DISC recruitment assay was used to assess levels of FLIP at the TRAIL-R2 DISC. Caspase activity, cell viability and apoptosis induction were assessed in CRC models treated with FLIP inhibitors alone and in combination with TRAIL or standard-of-care chemotherapeutics. Mechanism-of-action was assessed using caspase-8-targeted siRNA and FLIP overexpressing models. Results Using CRC cell line models, it was demonstrated that FLIP recruitment to the DISC is inhibited by FLIP inhibitors from the lead series. As a result, TRAIL-induced caspase-8 and caspase-3/7 activity were enhanced and increased levels of apoptosis cells were observed. Decreased cell viability was observed that was proportionate to the levels of apoptosis induced. Cell death triggered by FLIP inhibitors was shown to be caspase-8-dependent consistent with the expected mechanism-of-action. Importantly, inhibitors of FLIP also enhanced apoptosis induction in response to 5-Fluorouracil, oxaliplatin and SN38. Conclusion We have developed inhibitors of FLIP that decrease its recruitment to the TRAIL-R2 DISC and increase TRAIL-induced caspase activation and apoptosis. Moreover, these inhibitors synergise with 5-Fluorouracil, oxaliplatin and SN38, suggesting that this novel class of agents has therapeutic potential in CRC when used in conjunction with standard-of-care chemotherapeutic agents. Acknowledgements This work was supported by a Seeding Drug Discovery award from the Wellcome Trust (reference: 099470). Citation Format: Jennifer P. Fox, Joanna Majkut, Catherine Higgins, Zsuzsanna Nemeth, Adnan Malik, Christopher J. Scott, Peter Blurton, Ray J. Boffey, Trevor R. Perrior, Timothy Harrison, Daniel B. Longley. FLIP protein-protein interaction inhibitors enhance sensitivity of colorectal cancer cells to chemotherapy and TRAIL. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C5.

We have recently shown that inhalation of low, non-toxic doses of carbon monoxide (CO) is a potential therapeutic adjuvant treatment for lung cancer and prostate cancer (Cancer Research, 2013, Wegiel B et al). We found that CO doses of 100 ppm daily or twice per week were the most effective in suppressing A549 xenograft tumors growth, Ki67 expression and increased cleaved caspase-3 staining. Additionally, we found that inhibition of xenografts and KRAS-driven lung tumor growth in response to CO was associated with increased expression of M1 macrophage markers (CD86, CD197, RANTES) and decreased M2 markers (MMR) and HO-1 blockage. We demonstrated a direct interaction between HO-1 and Notch1. Further, that CO promotes Notch 1 cleavage as well as phosphorylation of ERK1/2 in the stroma cells, which are the markers of M1 polarization. Moreover, we demonstrated a significant correlation between low HO-1 expression and high p-ERK ½ expression in primary human lung cancers (n = 30 patients). In summary, we describe a mechanism by which CO affects cancer growth through regulation of macrophage polarization via Notch1 and Erk1/2 pathways. Citation Format: Zsuzsanna Nemeth, Eva Csizmadia, Lisa Vikstrom, Mailin Li, Kavita Bisht, Alborz Feizi, David Gallo, Leo Otterbein, Janos Fillinger, Balazs Dome, Daniel B. Costa, Barbara Wegiel. Carbon monoxide targets Notch1 and MAPK-ERK1/2 signaling pathways to block growth of lung carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 416. doi:10.1158/1538-7445.AM2015-416