• Hancock Peters posted an update 1 year, 7 months ago

    Reconstruction for soft-tissue sarcomas is complex and often uses soft-tissue flaps. To preserve critical structures, intraoperative radiotherapy (IORT) can be used to boost the total dose to these critical structures and close margins; however, there are limited data on the outcome of soft-tissue reconstruction in patients treated with IORT.

    Twenty patients received IORT with soft-tissue flap coverage. There were 14 tumors of the lower extremities and six of the upper, including seven free-flaps and 13 pedicle flaps. Mean preoperative and IORT doses were 49.4 Gy and 10.4 Gy, respectively, with a mean total dose of 59.8 Gy.

    Seven (35%) patients had a complication, most commonly an infection (n=4, 27%). Total flap loss occurred in one treated with pedicle flap. Four (20%) patients suffered a radiation-associated fracture. At the final follow-up, the mean Musculoskeletal Tumor Society Score was 75±11%.

    Complications and postoperative fractures were common with IORT, however, there were no cases requiring amputation.

    Complications and postoperative fractures were common with IORT, however, there were no cases requiring amputation.

    Chemokine receptor inhibition is an immunotherapy that modulates the innate arm of the immune system. Previous work in microsatellite-stable metastatic colorectal cancer showed an exploitive loop that could be successfully targeted via C-C-motive-chemokine-receptor 5 (CCR5) specific blocking, resulting in a selective anti-tumoral activation of macrophages. In the respective trial (MARACON trial, NCT01736813) the peripheral blood laboratory markers and cytokine values were measured over time. Little is known on their role as biomarkers or stratification parameters in immunotherapy trials.

    Systematic analyses of key laboratory parameters are presented, highlighting specific dynamics of lymphocyte and monocyte percentages, lactate dehydrogenase as well as interleukin-6 and interleukin-8 levels as parameters of a systemic inflammatory readout.

    Specific dynamical changes of lymphocyte and monocyte compositions were noted between different patients, showing a stabilization (or increase) versus decreased numbers over time for monocytes. While lactate dehydrogenase, interleukin-6 and interleukin-8 showed almost uniformly rising levels over time, the systemic monocyte patterns prompted a further evaluation. Stabilized or increasing monocyte percentages were associated with improved overall survival (Kaplan Meier analysis, p=0.025) and with induced overt radiologic necrosis in patients.

    The observed association between monocyte dynamics and imaging findings as well as overall survival suggests that analyses of dynamical parameters in the peripheral blood should be implemented in immunotherapy trials.

    The observed association between monocyte dynamics and imaging findings as well as overall survival suggests that analyses of dynamical parameters in the peripheral blood should be implemented in immunotherapy trials.

    Examine features of blood and lymphatic vessels in ovarian tumors and their significance to prognosis of ovarian cancer.

    A total of 139 women with epithelial ovarian tumors were included 86 malignant, 17 borderline and 36 benign. Density, percentage, mean size and number of blood microvessels in tumors were measured by immunohistochemistry with antibodies against CD34 and CD105. Lymphatic vessel density was assayed using the D2-40 antibody against podoplanin.

    Angiogenesis was most profuse in malignant tumors. Small size of lymph vessels predicted 26% shorter 5-year survival of ovarian cancer patients. Further, high percentage of lymphatic vessels in tumors was associated with lymph node metastasis, and high density with cancer recurrence. Lower number of microvessels, as assessed by CD34 staining, predicted shorter progression-free survival. Additionally, the large size of microvessels assessed by CD34 and the high number of vessels assessed by CD105 were related to residual tumor >1 cm at primary surgery and also, large vessel size was associated with stage III, as assessed by CD105 staining.

    CD34 and CD105 define different characteristics of microvessels. Parameters of lymph vessels may predict the prognosis of ovarian cancer.

    CD34 and CD105 define different characteristics of microvessels. Parameters of lymph vessels may predict the prognosis of ovarian cancer.

    Our phase III trial showed that biweekly docetaxel (D) is better tolerated than triweekly D in metastatic castration-resistant prostate cancer (mCRPC). The safety of biweekly cabazitaxel (CBZ) post-docetaxel was studied in mCRPC.

    Altogether, 60 patients received CBZ 16 mg/m

    i.v. on day 1 and day 14 of a 4-week cycle. The mean serum PSA levels were 305 ng/ml, and the mean age 67 years. The primary endpoint was safety according to CTCAEv4.0.

    A total of 255 4-week cycles of CBZ were administered. The most common grade 3/4 adverse events were neutropenia (16.7%), pain (13.3%), fatigue (10.0%), anemia (5.0%) and non-neutropenic infection (10.0%). PSA responses occurred in 10 patients (16.7%). Clinical benefit rate was 38.3% and median survival 10 months.

    Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.

    Biweekly CBZ is a well-tolerated treatment resulting in meaningful benefits for heavily pretreated mCRPC patients.

    Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Resistance to chemotherapy and side-effects remain a challenge for treating advanced and recurrent HCC. Therefore, there is an emerging need to develop new drugs to treat HCC.

    We evaluated the anti-growth activity of flavopereirine in HepG2 and Huh7 HCC cell lines. Bemcentinib Cell viability, cell-cycle profile, apoptosis, and autophagy-related protein expressions were analysed after flavopereirine treatment.

    Flavopereirine treatment induced G

    /G

    cell-cycle arrest, with an increase of sub-G

    cells detected at the higher concentration and longer exposure to flavopereirine in HCC cells. Intrinsic and extrinsic pathways were involved in flavopereirine-induced apoptosis, as demonstrated by an increase of cleaved caspase 8 and 9 by western blotting. An alteration of autophagy-related protein expression was also found after flavopereirine treatment.

    Taken together, the current results indicate that flavopereirine exhibits good anticancer activity in HCC cells.

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