Efficient enzymatic conversion of crystalline polysaccharides is crucial for an economically and environmentally sustainable bioeconomy but remains unfavorably inefficient. We describe an enzyme that ...acts on the surface of crystalline chitin, where it introduces chain breaks and generates oxidized chain ends, thus promoting further degradation by chitinases. This enzymatic activity was discovered and further characterized by using mass spectrometry and chromatographic separation methods to detect oxidized products generated in the absence or presence of H₂¹⁸O or ¹⁸O₂. There are strong indications that similar enzymes exist that work on cellulose. Our findings not only demonstrate the existence of a hitherto unknown enzyme activity but also provide new avenues toward more efficient enzymatic conversion of biomass.
Airway diseases such as chronic rhinosinusitis, asthma, and chronic obstructive pulmonary disorder are characterized by inflammation and remodeling. Among inflammatory and extracellular matrix ...regulatory cytokines, transforming growth factor‐beta (TGF‐β) stands central, as it possesses both important immunomodulatory and fibrogenic activities, and should be considered a key for understanding inflammation and remodeling processes. This review will briefly summarize the recent findings on the role of TGF‐β1, from the view points of inflammation and remodeling, and discuss the role of TGF‐β in the upper and lower airway diseases. This may reveal new perspectives in the understanding of airway inflammation and remodeling processes and may open innovative treatment strategies for the regulation of TGF‐β1.
Chinese rivers deliver about 5–10% of global freshwater input and 15–20% of the global continental sediment to the world ocean. We report the riverine fluxes and concentrations of major nutrients ...(nitrogen, phosphorus, and silicon) in the rivers of the contiguous landmass of China and Korea in the northeast Asia. The rivers are generally enriched with dissolved inorganic nitrogen (DIN) and depleted in dissolved inorganic phosphate (PO43−) with very high DIN: PO43− concentration ratios. DIN, phosphorus, and silicon levels and loads in rivers are mainly affected by agriculture activities and urbanization, anthropogenic activities and adsorption on particulates, and rock types, climate and physical denudation intensity, respectively. Nutrient transports by rivers in the summer are 3–4 times higher than those in the winter with the exception of NH4+. The flux of NH4+ is rather constant throughout the year due to the anthropogenic sources such as the sewer discharge. As nutrient composition has changed in the rivers, ecosystems in estuaries and coastal sea have also changed in recent decades. Among the changes, a shift of limiting nutrients from phosphorus to nitrogen for phytoplankton production with urbanization is noticeable and in some areas silicon becomes the limiting nutrient for diatom productivity. A simple steady-state mass-balance box model was employed to assess nutrient budgets in the estuaries. The major Chinese estuaries export <15% of nitrogen, <6% of phosphorus required for phytoplankton production and ~4% of silicon required for diatom growth in the Chinese Seas (Bohai, Yellow Sea, East China Sea, South China Sea). This suggests that land-derived nutrients are largely confined to the immediate estuaries, and ecosystem in the coastal sea beyond the estuaries is mainly supported by other nutrient sources such as regeneration, open ocean and atmospheric deposition.
It is estimated that around 15-30% of patients with early stage colon cancer benefit from adjuvant chemotherapy. We are currently not capable of upfront selection of patients who benefit from ...chemotherapy, which indicates the need for additional predictive markers for response to chemotherapy. It has been shown that the consensus molecular subtypes (CMSs), defined by RNA-profiling, have prognostic and/or predictive value. Due to postoperative timing of chemotherapy in current guidelines, tumor response to chemotherapy per CMS is not known, which makes the differentiation between the prognostic and predictive value impossible. Therefore, we propose to assess the tumor response per CMS in the neoadjuvant chemotherapy setting. This will provide us with clear data on the predictive value for chemotherapy response of the CMSs.
In this prospective, single arm, multicenter intervention study, 262 patients with resectable microsatellite stable cT3-4NxM0 colon cancer will be treated with two courses of neoadjuvant and two courses of adjuvant capecitabine and oxaliplatin. The primary endpoint is the pathological tumor response to neoadjuvant chemotherapy per CMS. Secondary endpoints are radiological tumor response, the prognostic value of these responses for recurrence free survival and overall survival and the differences in CMS classification of the same tumor before and after neoadjuvant chemotherapy. The study is scheduled to be performed in 8-10 Dutch hospitals. The first patient was included in February 2020.
Patient selection for adjuvant chemotherapy in early stage colon cancer is far from optimal. The CMS classification is a promising new biomarker, but a solid chemotherapy response assessment per subtype is lacking. In this study we will investigate whether CMS classification can be of added value in clinical decision making by analyzing the predictive value for chemotherapy response. This study can provide the results necessary to proceed to future studies in which (neo) adjuvant chemotherapy may be withhold in patients with a specific CMS subtype, who show no benefit from chemotherapy and for whom possible new treatments can be investigated.
This study has been registered in the Netherlands Trial Register (NL8177) at 11-26-2019, https://www.trialregister.nl/trial/8177 . The study has been approved by the medical ethics committee Utrecht (MEC18/712).
This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer.
Patients with thyroid ...cancer of any histology that was resistant or not appropriate for 131I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate partial response (PR) + stable response ≥12 weeks. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD), progression-free survival (PFS), overall survival, duration of response, and safety.
Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks 95% confidence interval (CI) 14.9–78.5. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%).
Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation.
NCT01164176.
Neoadjuvant therapy for pancreatic cancer Springfeld, Christoph; Ferrone, Cristina R; Katz, Matthew H G ...
Nature reviews. Clinical oncology,
05/2023, Letnik:
20, Številka:
5
Journal Article
Recenzirano
Patients with localized pancreatic ductal adenocarcinoma (PDAC) are best treated with surgical resection of the primary tumour and systemic chemotherapy, which provides considerably longer overall ...survival (OS) durations than either modality alone. Regardless, most patients will have disease relapse owing to micrometastatic disease. Although currently a matter of some debate, considerable research interest has been focused on the role of neoadjuvant therapy for all forms of resectable PDAC. Whilst adjuvant combination chemotherapy remains the standard of care for patients with resectable PDAC, neoadjuvant chemotherapy seems to improve OS without necessarily increasing the resection rate in those with borderline-resectable disease. Furthermore, around 20% of patients with unresectable non-metastatic PDAC might undergo resection following 4-6 months of induction combination chemotherapy with or without radiotherapy, even in the absence of a clear radiological response, leading to improved OS outcomes in this group. Distinct molecular and biological responses to different types of therapies need to be better understood in order to enable the optimal sequencing of specific treatment modalities to further improve OS. In this Review, we describe current treatment strategies for the various clinical stages of PDAC and discuss developments that are likely to determine the optimal sequence of multimodality therapies by integrating the fundamental clinical and molecular features of the cancer.
To provide evidence-based recommendations to oncologists and others on potentially curative therapy for patients with localized pancreatic cancer.
ASCO convened a panel of medical oncology, radiation ...oncology, surgical oncology, palliative care, and advocacy experts and conducted a systematic review of literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events.
Nine randomized controlled trials met the systematic review criteria.
A multiphase computed tomography scan of the abdomen and pelvis or magnetic resonance imaging should be performed for all patients to assess the anatomic relationships of the primary tumor and for the presence of intra-abdominal metastases. Baseline performance status, comorbidity profile, and goals of care should be evaluated and established. Primary surgical resection is recommended for all patients who have no metastases, appropriate performance and comorbidity profiles, and no radiographic interface between primary tumor and mesenteric vasculature. Preoperative therapy is recommended for patients who meet specific characteristics. All patients with resected pancreatic cancer who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of contraindications. Adjuvant chemoradiation may be offered to patients who did not receive preoperative therapy with microscopically positive margins (R1) after resection and/or who had node-positive disease after completion of 4 to 6 months of systemic adjuvant chemotherapy. Patients should have a full assessment of symptoms, psychological status, and social supports and should receive palliative care early. Patients who have completed treatment and have no evidence of disease should be monitored. Additional information is available at www.asco.org/guidelines/PCPC and www.asco.org/guidelineswiki.
Hollow TiO2 hemispheres for application in dye‐sensitized solar cells are prepared by means of rf‐sputtering onto colloidal templated substrates. After removing the organic templates by thermal ...decomposition, quasi‐ordered networks of hollow TiO2 hemispheres were formed. This approach should open up new opportunities for processing material architectures with high surface activity and effective charge transport for high performance photovoltaic and photoelectrochemical cells.
Psychological factors are thought to drive inter-patient variations in anaesthetic and analgesic requirements. This cross-sectional study investigated whether preoperative psychological factors can ...predict anaesthetic requirements and postoperative pain.
Before total thyroidectomy, 100 consecutive women completed the Spielberger's State–Trait Anxiety Inventory (STAI) and the pain sensitivity questionnaire (PSQ). Target-controlled propofol was administered for induction of anaesthesia, and sevoflurane–oxygen–air was given to maintain equal depths of anaesthesia, as determined by bispectral index (BIS) monitoring.
Patients with higher anxiety scores (state and trait) required greater amounts of propofol to reach light (BIS=85) and moderate (BIS=75) levels of sedation, but only trait anxiety was significantly associated with propofol requirements in reaching a deep level of sedation (BIS=65). The MAC-hour of sevoflurane was significantly correlated only with PSQ scores. The postoperative pain intensity was significantly correlated with both STAI and PSQ.
Preoperative anxiety and pain sensitivity are independent predictors of propofol and sevoflurane requirements in general anaesthesia. Anaesthetic and analgesic doses could be modified based on the patient's preoperative anxiety and pain sensitivity.
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