Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability...

Chlorin e6 Conjugated Poly(dopamine) Nanospheres as PDT/PTT Dual-Modal Therapeutic Agents for Enhanced Cancer Therapy.

Despite improvement in therapeutic strategies, median survival in advanced hepatocellular carcinoma (HCC) remains less than one year. Therefore, molecularly targeted compounds with less toxic profiles are needed. Xanthohumol (XN), a prenylated chalcone has been shown to have anti-proliferative effects in various cancers types in vitro. XN treatment in healthy mice and humans yielded favorable pharmacokinetics and bioavailability. Therefore, we determined to study the effects of XN and understand the mechanism of its action in HCC. The effects of XN on a panel of HCC cell lines were assessed for cell viability, colony forming ability, and cellular proliferation. Cell lysates were analyzed for pro-apoptotic (c-PARP and cleaved caspase-3) and anti-apoptotic markers (survivin, cyclin D1, and Mcl-1). XN concentrations of 5μM and above significantly reduced the cell viability, colony forming ability and also confluency of all four HCC cell lines studied. Furthermore, growth suppression due to apoptosis was evidenced by increased expression of pro-apoptotic and reduced expression of anti-apoptotic proteins. Importantly, XN treatment inhibited the Notch signaling pathway as evidenced by the decrease in the expression of Notch1 and HES-1 proteins. Ectopic expression of Notch1 in HCC cells reverses the anti-proliferative effect of XN as evidenced by reduced growth suppression compared to control. Taken together these results suggested that XN mediated growth suppression is appeared to be mediated by the inhibition of the Notch signaling pathway. Therefore, our findings warrants further studies on XN as a potential agent for the treatment for HCC.

/pdf/xanthohumol-inhibits-notch-signaling-and-induces-apoptosis-2ofni57n1q.pdf

Xanthohumol Inhibits Notch Signaling and Induces Apoptosis in Hepatocellular Carcinoma

Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, especially cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in hepatocellular carcinoma have not been extensively studied. The long non-coding RNA CASC2 (cancer susceptibility candidate 2) has been characterised as a tumour suppressor in endometrial cancer and gliomas. However, the role and function of CASC2 in hepatocellular carcinoma remain unknown. In this study, using quantitative real-time polymerase chain reaction, we confirmed that CASC2 expression was downregulated in 50 hepatocellular carcinoma cases (62%) and in hepatocellular carcinoma cell lines compared with the paired adjacent tissues and normal liver cells. In vitro experiments further demonstrated that overexpressed CASC2 decreased hepatocellular carcinoma cell proliferation, migration and invasion as well as promoted apoptosis via inactivating the mitogen-activated protein kinase signalling pathway. Our findings demonstrate that CASC2 could be a useful tumour suppressor factor and a promising therapeutic target for hepatocellular carcinoma.

Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer (BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization (TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC.

Liver resection for intermediate hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is well known for its aggressive nature and high recurrence rates. Alpha- fetoprotein (AFP) secreting tumors are more common in HCC. However, a few proportion of HCC do not produce AFP more than the basal level. AFP secreting tumors are more aggressive in nature since the ability of AFP to promote effective progression, growth, and metastasis of tumor. AFP also intervenes the immune system to evade the immune responses against cancer cells. AFP-producing tumors contain poorly differentiated cells similar to embryonic stem cells of liver mimicking rapid replication, proliferation, and AFP secretion by fetal liver. In this review, we highlight the crucial roles of AFP in immune evasion, aggressiveness, progression, and tumor biology of HCC.

Muir–Torre syndrome – An Indian case report

Das hepatozellulare Karzinom (HCC) ist mittlerweile die haufigste Todesursache bei Patienten mit Leberzirrhose. Es ist damit zurechnen, dass die Inzidenz in den kommenden Jahren auch in der westlichen Welt weiter steigt. Aufgrund einer unzureichenden Uberwachung von Risikopatienten wird die Erkrankung haufig erst in einem fortgeschrittenen Stadium diagnostiziert. Im Zusammenspiel mit der in den meisten Fallen zugrunde liegenden Leberzirrhose resultieren hieraus die eingeschrankten Behandlungsoptionen und die schlechte Prognose vieler Patienten. Umso wichtiger ist eine stadiengerechte Beurteilung und interdisziplinare Therapieentscheidung an erfahrenen Zentren. Unter Berucksichtigung der potenziell kurativen (Resektion, Lebertransplantation, lokale Ablation) und palliativen Therapieansatze (transarterielle Verfahren, Sorafenib) ist ein individualisiertes Gesamtkonzept moglich. Es ist zu hoffen, dass sich die Prognose von Patienten mit HCC durch eine verbesserte Pravention, konsequente Uberwachung, multimodale Therapiekonzepte und eine Ausweitung der personalisierten Medizin in naher Zukunft deutlich verbessern wird.

Therapie des hepatozellulären Karzinoms

A high alpha-fetoprotein slope prior to therapy correlates with poor prognosis of patients with hepatocellular carcinomas

Zielsetzung Die Pfortaderinfiltration ist eine häufige und schwerwiegende Komplikation bei Patienten mit HCC, die eine systemische Therapie gemäß der BCLC-Klassifikation impliziert. Unser Ziel war es daher, herauszufinden, ob eine Radiomics-Anlayse zum Erstdiagnosezeitpunkt das Auftreten einer Pfortaderinfiltration vorhersagen kann. 

Vorhersage von makrovaskulärer Infiltration beim HCC – eine Radiomics-Studie

Zielsetzung Das Milzvolumen wurde als relevanter prognostischer Faktor für Patienten mit hepatozellulärem Karzinom (HCC) vorgeschlagen. Um dieses routinemäßig zu bestimmen trainierten wir einen Deep-Learning-Algorithmus zur Milzsegmentierung bei CT-Untersuchungen. Anschließend wurde das Milzvolumen als Prognosefaktor hinsichtlich des Überlebens für Patienten mit HCC unter transarterieller Chemoembolisation (TACE) untersucht. 

KI-basierte Bestimmung des Milzvolumens als Risikofaktor für HCC-Patienten unter TACE-Therapie

Zielsetzung Um die Lehre während der Corona-Pandemie zu unterstützen, haben wir ein Flipped-Classroom-Konzept entwickelt, das einen speziellen Hybrid-Kurs in Thoraxradiologie umfasst, der sich sowohl aus Vor-Ort- als auch aus Online-Modulen zusammensetzt. Ziel dieser Studie war, die Einstellung der Studierenden zu innovativen Lehrkonzepten auszuwerten und zu prüfen, ob dieses spezielle Kursdesign das Wissen und das Verständnis der Studierenden für die Thoraxradiologie verbessern kann. 

Flipped-Classroom in der Thoraxradiologie: Ergebnisse einer prospektiven Studie

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