Influence of Thermal Treatment on the Composition of Alpinia officinarum Rhizome.

Alpinia officinarum is a representative of the Zingiberaceae family, which is known for its wide use in the food and pharmaceutical industries also due to its precious pharmacological potential. The major aim of the present study was to evaluate the influence of thermal treatment on the composition of the rhizome of Alpinia officinarum and its antioxidant activity. The fresh rhizome was subjected to various thermal treatment processes-boiling, frying and microwave heating during various time intervals-and their composition and antioxidant activity were determined using chromatographic (HPLC - High Performance Liquid Chromatography and HPLC-MS - High Performance Liquid Chromatography Mass Spectrometry) and spectrophotometric (DPPH and TPC - Total Phenolic Content) methods. Pinobanksin was the main compound found in the extract of the fresh rhizome (537.79 mg/kg), followed by galangin (197.7 mg/kg) and zingerone (185.5 mg/kg). The effect of thermal treatment on the rhizome composition was varied. In general, thermal processing significantly decreased the content of active compounds in the rhizome. However, there were some exceptions-boiling for 4 min significantly increased the content of pinobanksin (1162.4 mg/kg) and galangin (280.7 mg/kg), and microwave processing for 4 min increased the content of pinocembrin (213 mg/kg). It was found that boiling and microwave treatment significantly increased the antioxidant activity of the processed rhizomes.

Influence of Diet on the Bioavailability of Active Components from Zingiber officinale Using an In Vitro Digestion Model.

Ginger (Zingiber officinale Rosc.) is a plant known all over the world that is used as a spice and as an ingredient in drinks, dietary supplements, and cosmetics. The growing availability of its fresh rhizomes makes it even more likely to be used in the diet, mainly due to its beneficial health properties and high content of polyphenols (gingerols and shogaols). The main goal and motivation of the authors was to assess the bioavailability of active substances contained in the extract from ginger rhizomes in the presence of various types of diets using the in vitro digestion method, enabling simulation of the processes occurring during the digestion and absorption of metabolites in the small intestine. For the qualitative and quantitative analyses, the HPLC-MS (High Performance Liquid Chromatography-Mass Spectrometry) and HPLC (High Performance Liquid Chromatography) techniques were used, respectively. Based on the obtained results, it was found that the best bioavailability of the selected ginger polyphenols (6-gingerol, 8-gingerdione, 8-shogaol, and 10-gingerdione) was estimated for a high-fiber diet, while the weakest results were obtained for standard and basic diets. In the case of the high-fiber diet, the bioavailability of the mentioned compounds was estimated as 33.3, 21.4, 6.73, and 21.0%, while for the basic diet, it was only 21.3, 5.3, 2.0, and 1.0%, respectively.

BAZ2A-mediated repression via H3K14ac-marked enhancers promotes prostate cancer stem cells.

Prostate cancer (PCa) is one of the most prevalent cancers in men. Cancer stem cells are thought to be associated with PCa relapse. Here, we show that BAZ2A is required for PCa cells with a cancer stem-like state. BAZ2A genomic occupancy in PCa cells coincides with H3K14ac-enriched chromatin regions. This association is mediated by BAZ2A-bromodomain (BAZ2A-BRD) that specifically binds H3K14ac. BAZ2A associates with inactive enhancers marked by H3K14ac and repressing transcription of genes frequently silenced in aggressive and poorly differentiated PCa. BAZ2A-mediated repression is also linked to EP300 that acetylates H3K14ac. BAZ2A-BRD mutations or treatment with inhibitors abrogating BAZ2A-BRD/H3K14ac interaction impair PCa stem cells. Furthermore, pharmacological inactivation of BAZ2A-BRD impairs Pten-loss oncogenic transformation of prostate organoids. Our findings indicate a role of BAZ2A-BRD in PCa stem cell features and suggest potential epigenetic-reader therapeutic strategies to target BAZ2A in aggressive PCa.

TIP5 primes prostate luminal cells for the oncogenic transformation mediated by PTEN-loss.

Prostate cancer (PCa) is the second leading cause of cancer death in men. Its clinical and molecular heterogeneities and the lack of in vitro models outline the complexity of PCa in the clinical and research settings. We established an in vitro mouse PCa model based on organoid technology that takes into account the cell of origin and the order of events. Primary PCa with deletion of the tumor suppressor gene PTEN (PTEN-del) can be modeled through Pten-down-regulation in mouse organoids. We used this system to elucidate the contribution of TIP5 in PCa initiation, a chromatin regulator that is implicated in aggressive PCa. High TIP5 expression correlates with primary PTEN-del PCa and this combination strongly associates with reduced prostate-specific antigen (PSA) recurrence-free survival. TIP5 is critical for the initiation of PCa of luminal origin mediated by Pten-loss whereas it is dispensable once Pten-loss mediated transformation is established. Cross-species analyses revealed a PTEN gene signature that identified a group of aggressive primary PCas characterized by PTEN-del, high-TIP5 expression, and a TIP5-regulated gene expression profile. The results highlight the modeling of PCa with organoids as a powerful tool to elucidate the role of genetic alterations found in recent studies in their time orders and cells of origin, thereby providing further optimization for tumor stratification to improve the clinical management of PCa.

TGFß signaling limits lineage plasticity in prostate cancer.

Although treatment options for localized prostate cancer (CaP) are initially effective, the five-year survival for metastatic CaP is below 30%. Mutation or deletion of the PTEN tumor suppressor is a frequent event in metastatic CaP, and inactivation of the transforming growth factor (TGF) ß signaling pathway is associated with more advanced disease. We previously demonstrated that mouse models of CaP based on inactivation of Pten and the TGFß type II receptor (Tgfbr2) rapidly become invasive and metastatic. Here we show that mouse prostate tumors lacking Pten and Tgfbr2 have higher expression of stem cell markers and genes indicative of basal epithelial cells, and that basal cell proliferation is increased compared to Pten mutants. To better model the primarily luminal phenotype of human CaP we mutated Pten and Tgfbr2 specifically in luminal cells, and found that these tumors also progress to invasive and metastatic cancer. Accompanying the transition to invasive cancer we observed de-differentiation of luminal tumor cells to an intermediate cell type with both basal and luminal markers, as well as differentiation to basal cells. Proliferation rates in these de-differentiated cells were lower than in either basal or luminal cells. However, de-differentiated cells account for the majority of cells in micro-metastases consistent with a preferential contribution to metastasis. We suggest that active TGFß signaling limits lineage plasticity in prostate luminal cells, and that de-differentiation of luminal tumor cells can drive progression to metastatic disease.

Quality of life and occurrence of depression under chemotherapy in patients suffering from lung carcinoma.

INTRODUCTION AND OBJECTIVE: In Poland, lung carcinoma is the most frequent malignant neoplasm in men and the third most frequent in women. The neoplastic disease causes enormous psychic stress and may lead to depressive reactions. The purpose of this research was to assess the quality of life and the occurrence of depression in patients suffering from lung neoplasms and undergoing chemotherapy. MATERIALS AND METHOD: The research covered 102 patients (test group TG) with lung carcinoma and undergoing chemotherapy. In the research, standardised questionnaires: EORTC-QLQ-C30, Beck Depression Inventory and a matrix developed by the researcher were applied. The control group (CG) consisted of 60 healthy people who were examined by the Beck Depression Inventory. RESULTS: A highly statistically significant dependency was found (p<0.01) between the general quality of life and the occurrence of depression. 51.5% of those examined with a very low level of general quality of life had the symptoms of severe depression. Those examined who had a very high level of general quality of life did not have features of severe depression. A statistically significant dependency (p<0.01) was ascertained between the occurrence of depression and the health condition of those examined. CONCLUSIONS: Depression symptoms occur more frequently and with greater intensity in patients suffering from lung neoplasm, compared to the group of healthy people (p<0.01). A statistically significant connection between marital status, place of residence, and assessment of quality of life was found out (p<0.05).

Prostate cancer induced by loss of Apc is restrained by TGFß signaling.

Recent work with mouse models of prostate cancer (CaP) has shown that inactivation of TGFß signaling in prostate epithelium can cooperate with deletion of the Pten tumor suppressor to drive locally aggressive cancer and metastatic disease. Here, we show that inactivating the TGFß pathway by deleting the gene encoding the TGFß type II receptor (Tgfbr2) in combination with a deletion of the Apc tumor suppressor gene specifically in mouse prostate epithelium, results in the rapid onset of invasive CaP. Micro-metastases were observed in the lymph nodes and lungs of a proportion of the double mutant mice, whereas no metastases were observed in Apc single mutant mice. Prostate-specific Apc;Tgfbr2 mutants had a lower frequency of metastasis and survived significantly longer than Pten;Tgfbr2 double mutants. However, all Apc;Tgfbr2 mutants developed invasive cancer by 30 weeks of age, whereas invasive cancer was rarely observed in Apc single mutant animals, even by one year of age. Further comparison of the Pten and Apc models of CaP revealed additional differences, including adenosquamous carcinoma in the Apc;Tgfbr2 mutants that was not seen in the Pten model, and a lack of robust induction of the TGFß pathway in Apc null prostate. In addition to causing high-grade prostate intra-epithelial neoplasia (HGPIN), deletion of either Pten or Apc induced senescence in affected prostate ducts, and this restraint was overcome by loss of Tgfbr2. In summary, this work demonstrates that TGFß signaling restrains the progression of CaP induced by different tumor suppressor mutations, suggesting that TGFß signaling exerts a general tumor suppressive effect in prostate.