Targeting Aging with Functional Food: Pasta with Opuntia Single-Arm Pilot Study

Rejuvenation Research , Vol. 0, No. 0.


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Gastrointestinal perforation related to lenvatinib, an anti-angiogenic inhibitor that targets multiple receptor tyrosine kinases, in a patient with metastatic thyroid cancer

Summary

Lenvatinib, a novel potent multikinase inhibitor, was approved for the treatment of radioiodine-refractory differentiated thyroid cancer based on results from phase III trial (SELECT study). Thyroid cancer is a diverse disease that includes anaplastic thyroid cancer (ATC), which the most aggressive form of the disease, although it accounts for <2% of all thyroid cancers. Current treatments for ATC have limited efficacy. We report the case of a woman with recurrent well-differentiated papillary carcinoma of the thyroid that had transformed into ATC who developed a perforation of the small intestine secondary to a marked effect of lenvatinib. She received lenvatinib (24 mg once a day) at only two doses during two weeks due to pleurodesis with talc for malignant pleural effusion. Eventually, she developed peritonitis due to the perforation and died of sepsis. However, an autopsy revealed marked efficacy of lenvatinib for ATC at a metastatic site in the small intestine despite limited exposure to the drug. Here, we report on our experience with lenvatinib treatment and gastrointestinal perforation concerning anti-angiogenic therapy.

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Mechanisms and implications of ADAR-mediated RNA editing in cancer

Publication date: 28 December 2017
Source:Cancer Letters, Volume 411
Author(s): Chen Wang, Jun Zou, Xiangyi Ma, Edward Wang, Guang Peng
Adenosine deaminases acting on RNA (ADARs) are enzymes that catalyze the conversion of adenosine (A) to inosine (I) in double-stranded RNAs. Inosine exhibits similar properties as guanosine. As a result, A-to-I editing has a great impact on edited RNAs, not only affecting the base pairing properties, but also altering codons after translation. A-to-I editing are known to mediate and diversify transcripts. However, the overall biological effect of ADARs are still largely unknown. Aberrant ADAR activity and editing dysregulation are present in a variety of cancers, including hepatocellular carcinoma, chronic myelogenous leukemia, glioblastoma and melanoma. ADAR-mediated A-to-I editing can influence uncontrolled nucleotide changes, resulting in susceptibility of cells to developmental defects and potential carcinogenicity. A deeper understanding of the biological function of ADARs may provide mechanistic insights in the development of new cancer therapy. Here, we discuss recent advances in research on ADAR in detail including the structure and function of ADARs, the biochemistry of ADAR-mediated RNA editing, and the relevance of ADAR proteins in cancer.



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HSP90 inhibitor (NVP-AUY922) enhances the anti-cancer effect of BCL-2 inhibitor (ABT-737) in small cell lung cancer expressing BCL-2

Publication date: 28 December 2017
Source:Cancer Letters, Volume 411
Author(s): Hannah Yang, Mi-Hee Lee, Intae Park, Hanwool Jeon, Junyoung Choi, Seyoung Seo, Sang-We Kim, Gou Young Koh, Kang-Seo Park, Dae Ho Lee
Small cell lung cancer (SCLC) cannot be efficiently controlled using existing chemotherapy and radiotherapy approaches, indicating the need for new therapeutic strategies. Although ABT-737, a B-cell lymphoma-2 (BCL-2) inhibitor, exerts anticancer effects against BCL-2-expressing SCLC, monotherapy with ABT-737 is associated with limited clinical activity because of the development of resistance and toxicity. Here, we examined whether combination therapy with ABT-737 and heat shock protein 90 (HSP90) inhibitor NVP-AUY922 exerted synergistic anticancer effects on SCLC. We found that the combination of ABT-737 and NVP-AUY922 synergistically induced the apoptosis of BCL-2-expressing SCLC cells. NVP-AUY922 downregulated the expression of AKT and ERK, which activate MCL-1 to induce resistance against ABT-737. The synergistic effect was also partly due to blocking NF-κB activation, which induces anti-apoptosis protein expressions. However, interestingly, targeting BCL-2 and MCL-1 or BCL2 and NF-κB did not induce the cytotoxicity. In conclusion, our study showed that combination of BCL2 inhibitor with HSP90 inhibitor increased activity in in vitro and in vivo study in only BCL-2 expressing SCLC compared to either single BCL2 inhibitor or HSP inhibitor. The enhanced activity might be led by blocking several apoptotic pathways simultaneously rather than a specific pathway.



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Integrating T cell metabolism in cancer immunotherapy

Publication date: 28 December 2017
Source:Cancer Letters, Volume 411
Author(s): Erica Dugnani, Valentina Pasquale, Carlotta Bordignon, Adriana Canu, Lorenzo Piemonti, Paolo Monti
Activation and maintenance of the T cell response occurs concurrently with metabolic reprogramming. This ensures the T cell response is supported by sufficient energy and substrates necessary for cell survival, growth and proliferation. Different metabolic programs are associated with differentiation into different cell subsets, effector function and development of long-lasting memory. This provides an opportunity to improve the T cell response through manipulation of metabolism, which is instrumental to ameliorate the current protocols for cancer immunotherapy. Using drugs and molecules targeting selective metabolic pathways it is now possible to generate T cells that can mount a durable and stable anti-tumor response. On the other hand, cancer cells can take advantage of the metabolic requirements of T cells to evade the immune response. In this brief review we discuss recent findings of T cell metabolism in quiescence and activation, how the tumor microenvironment can affect T cell metabolism, and how T cell metabolism can be manipulated to improve the T cell response to tumors.



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Pharmacological evidence for the bone-autonomous contribution of the NFκB/β-catenin axis to breast cancer related osteolysis

Publication date: 1 December 2017
Source:Cancer Letters, Volume 410
Author(s): Silvia Marino, Ryan T. Bishop, John G. Logan, Patrick Mollat, Aymen I. Idris
The NFκB signaling pathway is implicated in breast cancer and bone metastasis. However, the bone-autonomous contribution of NFκB to breast cancer-induced osteolysis is poorly understood. Here, we report that pretreatment of osteoblasts with the sesquiterpene lactone Parthenolide (PTN), a verified NFκB inhibitor, prior to exposure to conditioned medium from human and mouse breast cancer cell lines enhanced osteoblast differentiation and reduced osteoblast ability to stimulate osteoclastogenesis. PTN prevented breast cancer-induced osteoclast formation and reduced the ability of breast cancer cells to prolong osteoclast survival and to inhibit osteoclast apoptosis. In vivo, administration of PTN in immuno-competent mice reduced osteolytic bone loss and skeletal tumour growth following injection of the syngeneic 4T1-BT1 cells and reduced local osteolysis caused by conditioned medium from human and mouse osteotropic breast cancer cell lines. Mechanistic studies revealed that NFκB inhibition by PTN in osteoblasts and osteoclasts was accompanied by a significant increase in β-catenin activation and expression. Collectively, these results raise the possibility that combined targeting of NFκB and β-catenin signalling in the tumour microenvironment may be of value in the treatment of breast cancer related osteolysis.



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Fundraiser for Syrian refugee to practice dentistry in Norwich

Anas, a refugee who fled Syria in 2015, is raising funds to help him convert his dentistry qualification into one which is recognised in the UK. Before leaving his home after being targetted by conflict sides in Syria, who were aiming at medical proffesionals, Anas studied at the University of Damascus.

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Effect of desiccant system on thin layer drying kinetics of corn

Abstract

Drying is one of the most important post-harvest processes for reducing the moisture content of agricultural products and improving their performance has obvious benefits. Most dryers are convective type in which hot air is used for reduction of product moisture content. Effect of adding a desiccant unit to a re-circulating convective dryer on thin layer drying kinetics of corn kernels is reported here. The influence of the desiccant unit, drying temperature and flow rate on drying time, moisture diffusivity coefficient and reactivation energy were investigated. The experiments were conducted at air temperatures of 50, 60 and 70 °C and flow rates of 1, 1.4 and 1.8 kg/min with and without the desiccant unit. Results showed that the use of the desiccant wheel decreased drying time by 9.75% and increased drying rate by 7.85%. Application of a Logarithmic model for fitting the data, while being simple, resulted in good statistical indexes (R² and RMSE). Moisture diffusivity coefficient was obtained to be in the 3.47258 × 10⁻¹¹ to 8.18826 × 10⁻¹¹ m²/s range, while activation energy varied between 14.2931 and 17.6770 kJ/mol on the average. Therefore, utilization of the desiccant unit accelerates moisture extraction from corn samples.

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The role of cognitive reserve in cognitive aging: what we can learn from Parkinson’s disease

Abstract

Parkinson's disease (PD) typically occurs in elderly people and some degree of cognitive impairment is usually present. Cognitive reserve (CR) theory was proposed to explain the discrepancy between the degree of brain pathologies and clinical manifestations. We administered a comprehensive neuropsychological battery to 35 non-demented participants affected by PD. All participants underwent also the Cognitive Reserve Index questionnaire and the Brief Intelligence Test as proxies for CR. Relationships between CR and cognitive performance were investigated by linear regression analyses, adjusting for significant confounding factors. At linear regression analyses, higher CR scores were independently associated with a better performance on Word Fluency (p ≤ 0.04) and Digit Span (backward) (p ≤ 0.02); no associations were observed between CR and other cognitive tests. Our data provide empirical support to the relation between CR and cognitive impairment in PD. In particular, this study suggests that CR may have greater effects on the cognitive areas mostly affected in PD as executive functions.

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Hypoxic volume evaluated by 18F-fluoromisonidazole positron emission tomography (FMISO-PET) may be a prognostic factor in patients with oral squamous cell carcinoma: preliminary analyses

This study evaluated the relationships between these PET parameters and 5-year survival in OSCC patients. Twenty-three patients (age 42 –84 years; 15 male, eight female) with OSCC underwent FMISO- and 18F-fluoro-2-deoxyglucose (FDG)-PET computed tomography before surgery. (Source: International Journal of Oral and Maxillofacial Surgery)

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The trajectory of positive psychological change in a head and neck cancer population

A stressful event may be sufficient to challenge a strongly held set of assumptions about the world and the self. In some people this may lead to post-traumatic stress disorder (PTSD) and in others to positive psychological change (PPC), whereby a person 's reactions to the challenge are beneficial. Little research has investigated PPC in people who have had head and neck cancer (HNC). The aim of this study was to identify demographic, clinical, and psychological factors associated with PPC over time. (Source: International Journal of Oral and Maxillofacial Surgery)

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SPECT bone scintigraphy for the assessment of condylar growth activity in mandibular asymmetry: is it accurate?

The comparison of serial radiographs and clinical photographs is considered the current accepted standard for the diagnosis of active condylar hyperplasia in patients with facial asymmetry. Single photon emission computed tomography (SPECT) has recently been proposed as an alternative method. SPECT can be interpreted using three reported methods absolute difference in uptake, uptake ratio, and relative uptake. SPECT findings were compared to those from serial comparisons of radiographs and clinical photographs taken at the time of SPECT and a year later; the sensitivities and specificities were determined. (Source: International Journal of Oral and Maxillofacial Surgery)

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Intrasinusal locking technique: a novel use of the ring block technique at sinus perforations for simultaneous implant placement

Ten patients who underwent sinus lift surgery with simultaneous implant placement using the intrasinusal locking technique were evaluated retrospectively. All patients were scheduled for sinus floor elevation procedures with simultaneous implant placement. Schneiderian membrane perforation occurred during the lifting procedure, and conventional methods failed to repair the perforation. Therefore, an autogenous bone ring was placed at the base of the maxillary sinus and was locked to the alveolar crest with a dental implant. (Source: International Journal of Oral and Maxillofacial Surgery)

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Erythrokeratoderma - a manifestation associated with multiple types of ichthyoses with different gene defects

Erythrokeratoderma (OMIM #133200) refers to a group of closely related disorders of cornification manifesting with hyperkeratotic, often transient and migratory, erythematous figurate plaques with sharply demarcated borders that typically develop in early childhood with or without palmoplantar involvement.¹ Erythrokeratodermas have been historically classified into the two main categories: (a) erythrokeratodermia variabilis et progressiva (EKVP, also known as erythrokeratoderma figurata variabilis and Mendes da Costa disease), and (b) progressive symmetric erythrokeratoderma (PSEK, also known as Gottron syndrome).

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The optimal regimen of brentuximab vedotin for CD30+ cutaneous lymphoma: Are we there yet?

Brentuximab vedotin (BV) is an anti-CD30 antibody–drug conjugate that is approved for refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma. In the ALCANZA trial, the proportion of CD30+ cutaneous T-cell lymphoma (CTCL) patients achieving an objective response lasting at least 4 months was 56.3% with BV versus 12.5% with conventional therapy (oral methotrexate or bexarotene), and progression-free survival, complete response rate and improvement in symptom burden were significantly improved.¹ As in previous studies, 1.8 mg/kg dose was administered every 3 weeks in this study.^1,2 We routinely use this regimen that has been well studied in clinical trials, starting with 1.8 mg/kg and decrease to 1.2 mg/kg if needed. The safety profile for BV is similar to conventional therapies and although peripheral neuropathy occurs in 67%, it usually resolves or improves after cessation or completion of treatment.¹

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Sperm counts, testicular cancers, and the environment

A recent meta-analysis by Levine and colleagues1 showing significant declines in sperm counts among men in the Western world caught considerable media attention.2 The Levine study followed a similar...

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Comparison of postoperative outcomes among patients treated by male and female surgeons: a population based matched cohort study

Objective To examine the effect of surgeon sex on postoperative outcomes of patients undergoing common surgical procedures.Design Population based, retrospective, matched cohort study from 2007 to...

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#ILookLikeASurgeon: embracing diversity to improve patient outcomes

Over the two years since it began1 #ILookLikeASurgeon, an online campaign celebrating women in surgery, has been included in over 150 000 tweets by over 35 000 users, making nearly a billion...

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Improving patient outcomes after surgery

Factors associated with variation in outcome after surgery have been a topic of major interest for the past 20 years. By far the most explored is the relation between case volume and outcome....

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PD-1 blockade prevents the development and progression of carcinogen-induced oral premalignant lesions

Oral squamous cell carcinoma (OSCC) is preceded by progressive oral premalignant lesions (OPLs). Therefore, therapeutic strategies that prevent malignant progression of OPLs are expected to reduce the incidence of OSCC development. Immune checkpoint inhibitors that target the interaction of programmed death receptor 1 (PD-1) on T cells with the PD-1 ligand PD-L1 on cancer cells have been shown to extend the survival of patients with advanced OSCC. Here, we used the 4-Nitroquinoline-1-oxide (4-NQO) mouse model of oral carcinogenesis to test the hypothesis that PD-1 blockade may control the progression of OPLs. Mice were exposed to 4-NQO in their drinking water and then randomly assigned to two treatment groups that received either a blocking antibody for PD-1 or a control IgG. We found that anti-PD-1 treatment significantly reduced the number of oral lesions that developed in these mice, and prevented malignant progression. Low-grade dysplastic lesions responded to PD-1 blockade with a significant increase in the recruitment of CD8+ and CD4+ T cells and the accumulation of CTLA-4+ T cells in their microenvironment. Notably, PD-1 inhibition was accompanied by induction of interferon-, STAT1 activation and the production of the T cell effector granzyme B in infiltrating cells, and by the induction of apoptosis in the epithelial cells of the oral lesions, suggesting that T cell activation mediates the immunopreventive effects of anti-PD-1. These results support the potential clinical benefit of PD-1 immune checkpoint blockade to prevent OSCC development and progression and suggest that CTLA-4 inhibitors may enhance the preventive effects of anti-PD-1.

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