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Get ready for a rollercoaster ride with this week's guest, Jocelyn Kervin! She's not just rocking the high school music scene but also strikes a chord in the world of Multiple Myeloma awareness. Imagine going from running 5K races around Toronto to receiving a life-altering diagnosis at 43 of a disease you've never even heard of!We chat about everything from the rapid advancements in MM treatments to the urgent need for early diagnosis. Once considered an "older person's cancer," MM is making its appearance in younger populations, and Jocelyn is here to say it's time for a wake-up call, especially for family physicians and the general public.Oh, and you can't miss the jaw-dropping twist-how a fractured rib during sex led Jocelyn to the X-ray that quite literally saved her life!Join the post-episode conversation over on Discord! https://discord.gg/expeUDN

Get ready for a rollercoaster ride with this week's guest, Jocelyn Kervin! She's not just rocking the high school music scene but also strikes a chord in the world of Multiple Myeloma awareness. Imagine going from running 5K races around Toronto to receiving a life-altering diagnosis at 43 of a disease you've never even heard of!We chat about everything from the rapid advancements in MM treatments to the urgent need for early diagnosis. Once considered an "older person's cancer," MM is making its appearance in younger populations, and Jocelyn is here to say it's time for a wake-up call, especially for family physicians and the general public.Oh, and you can't miss the jaw-dropping twist-how a fractured rib during sex led Jocelyn to the X-ray that quite literally saved her life!Join the post-episode conversation over on Discord! https://discord.gg/expeUDN

Get ready for a rollercoaster ride with this week's guest, Jocelyn Kervin! She's not just rocking the high school music scene but also strikes a chord in the world of Multiple Myeloma awareness. Imagine going from running 5K races around Toronto to receiving a life-altering diagnosis at 43 of a disease you've never even heard of!We chat about everything from the rapid advancements in MM treatments to the urgent need for early diagnosis. Once considered an "older person's cancer," MM is making its appearance in younger populations, and Jocelyn is here to say it's time for a wake-up call, especially for family physicians and the general public.Oh, and you can't miss the jaw-dropping twist-how a fractured rib during sex led Jocelyn to the X-ray that quite literally saved her life!Join the post-episode conversation over on Discord! https://discord.gg/expeUDN

Get ready for a rollercoaster ride with this week's guest, Jocelyn Kervin! She's not just rocking the high school music scene but also strikes a chord in the world of Multiple Myeloma awareness. Imagine going from running 5K races around Toronto to receiving a life-altering diagnosis at 43 of a disease you've never even heard of!We chat about everything from the rapid advancements in MM treatments to the urgent need for early diagnosis. Once considered an "older person's cancer," MM is making its appearance in younger populations, and Jocelyn is here to say it's time for a wake-up call, especially for family physicians and the general public.Oh, and you can't miss the jaw-dropping twist-how a fractured rib during sex led Jocelyn to the X-ray that quite literally saved her life!Join the post-episode conversation over on Discord! https://discord.gg/expeUDN

This article is from Korean Journal of Pathology , volume 47 . Abstract Background: Absolute lymphocyte count (ALC) in peripheral blood has recently been reported to be an independent prognostic factor in multiple myeloma (MM). Previous studies indicated that the absolute monocyte count (AMC) in peripheral blood reflects the state of the tumor microenvironment in lymphomas. Neither the utility of the AMC nor its relationship with ALC has been studied in MM. Methods: The prognostic value of ALC, AMC, and the ALC/AMC ratio at the time of diagnosis was retrospectively examined in 189 patients with MM. Results: On univariate analysis, low ALC (

Through analysis of the chromatin and transcriptional landscape of Multiple Myeloma (MM) and other tumors, this project has endeavored to provide an explanatory mechanism for how treatment with inhibitors of chromatin regulators can selectively target oncogene transcription, and to understand how chromatin and transcription are altered to promote tumorigenesis. Here we report the discoveries that BET bromodomains are required to communicate enhancer mediated pro-inflammatory signal dependent transduction (Brown et al., 2014), that translocations of the IgH enhancer to the MYC locus in MM expose both enhancer driven and MYC/E2F driven regulatory programs to BET bromodomain inhibition (Fulciniti et al., submitted), and that master transcription factors co-operate with one another and BET bromodomains to establish oncogenic state in MM and other tumors (Lin et al., submitted). These efforts have yielded insights into the dynamic transcriptional control of oncogenic cell state, the development of novel and extendable experimental and computational approaches, and therapeutic insights into the consequences of systemic in vivo BET bromodomain inhibition.

Through analysis of the chromatin and transcriptional landscape of Multiple Myeloma (MM) and other tumors, this project has endeavored to provide an explanatory mechanism for how treatment with inhibitors of chromatin regulators can selectively target oncogene transcription, and to understand how chromatin and transcription are altered to promote tumorigenesis. Here we report the discoveries that BET bromodomains are required to communicate enhancer mediated pro-inflammatory signal dependent transduction (Brown et al., 2014), that translocations of the IgH enhancer to the MYC locus in MM expose both enhancer driven and MYC/E2F driven regulatory programs to BET bromodomain inhibition (Fulciniti et al., submitted), and that master transcription factors co-operate with one another and BET bromodomains to establish oncogenic state in MM and other tumors (Lin et al., submitted). These efforts have yielded insights into the dynamic transcriptional control of oncogenic cell state, the development of novel and extendable experimental and computational approaches, and therapeutic insights into the consequences of systemic in vivo BET bromodomain inhibition.

This article is from Oncotarget , volume 4 . Abstract In the era of new and mostly effective therapeutic protocols, multiple myeloma still tends to be a hard-to-treat hematologic cancer. This hallmark of the disease is in fact a sequel to drug resistant phenotypes persisting initially or emerging in the course of treatment. Furthermore, the heterogeneous nature of multiple myeloma makes treating patients with the same drug challenging because finding a drugable oncogenic process common to all patients is not yet feasible, while our current knowledge of genetic/epigenetic basis of multiple myeloma pathogenesis is outstanding. Nonetheless, bone marrow microenvironment components are well known as playing critical roles in myeloma tumor cell survival and environment-mediated drug resistance happening most possibly in all myeloma patients. Generally speaking, however; real mechanisms underlying drug resistance in multiple myeloma are not completely understood. The present review will discuss the latest findings and concepts in this regard. It reviews the association of important chromosomal translocations, oncogenes (e.g. TP53) mutations and deranged signaling pathways (e.g. NFκB) with drug response in clinical and experimental investigations. It will also highlight how bone marrow microenvironment signals (Wnt, Notch) and myeloma cancer stem cells could contribute to drug resistance in multiple myeloma.

This article is from Current Cancer Drug Targets , volume 12 . Abstract MicroRNAs (miRNAs) recently emerged with a key role in multiple myeloma (MM) pathophysiology and are considered important regulators of MM cell growth and survival. Since miRNAs can act either as oncogenes or tumour suppressors, the potential of targeting the miRNA network arises as a novel therapeutic approach for human cancer. Potential strategies based on miRNA therapeutics basically rely on miRNA inhibition or miRNA replacement approaches and take benefit respectively from the use of antagomirs or synthetic miRNAs as well as from lipid-based nanoparticles which allow an efficient miRNA-delivery. The availability of experimental in vivo platforms which recapitulate the growth of MM cells within the specific human bone marrow microenvironment in immunocompromised mice (SCID-hu and SCID-synth-hu) provides powerful systems for development of miRNA-based therapeutics in MM. Preliminary findings on the anti-MM activity of synthetic miRNAs in such experimental models offer a proof-of-principle that miRNA therapeutics is a promising opportunity for this still incurable disease representing the rationale for a new venue of investigation in this specific field.

Maggie Garcia RN and Naturopathic Practitioner is seeking for a cure for her medically diagnosed cancerous condition of multiple myeloma. According to current medical savants multiple myeloma is a cancer that forms in a type of white blood cell called a plasma cell. Healthy plasma cells help you fight infections by making antibodies that recognize and attack germs. In multiple myeloma, cancerous plasma cells accumulate in the bone marrow and crowd out healthy blood cells. According to Dr. Robert O. Young plasma cells are being created to fight outfection which is the increased amounts of metabolic, dietary, and environmental acidic waste causing cellular breakdown and the pleomorphic birth of microorganisms or germs. The real cause of multiple myeloma is decompensated acidosis of the interstitial fluids of the Interstitium which can only be reversed with an alkaline electron rich lifestyle and diet. To learn more read The pH Miracle revised and updated by Dr. Robert O Young, DSc, PhD and Dr. Galina Migalko MD. www.drrobertyoung.com/blog and [email protected] Robert O Young CPT, MSc, DSc, PhD, Naturopathic Practitioner, Commissioner International Tribunal of Natural Justicewww.drrobertyoung.com - CV www.drrobertyoung.com/blog - scientific blog https://phoreveryoung.wordpress.com/ -  https://www.youtube.com/c/RobertYoung555/playlists - 1000's of videos to watch www.universalmedicalimaging.com - non-invasive medical diagnostics www.phmiracleproducts.com - alkalizing products www.phmriacleretreat.com - treatment centerswww.thriveon.com - World premier documentary https://www.amazon.com/kindle-dbs/entity/author/B001ILKCSU?_encoding=UTF8&node=283155&offset=0&pageSize=12&searchAlias=stripbooks&sort=author-sidecar-rank&page=1&langFilter=default#formatSelectorHeader  - Books by Dr. Robert O Young https://www.instagram.com/drrobertyoung/ - instagram https://www.linkedin.com/in/robert-young-bb650311b/ - linkedinhttps://twitter.com/settings/profile - twitter https://www.facebook.com/profile.php?id=100007707879435 - Facebook

This article is from Experimental and Therapeutic Medicine , volume 7 . Abstract Studies have shown that the bortezomib-based retreatment of patients with multiple myeloma (MM) may prolong control of the disease. The optimal duration of bortezomib-based retreatment in relapsed or refractory MM is unknown. The present retrospective study evaluated the efficacy and safety of short-course bortezomib-based retreatment in patients who had received bortezomib-thalidomide-dexamethasone (VTD) treatment for the initial therapy of newly diagnosed MM. The clinical records of 20 patients who had received short-course bortezomib-based retreatment in a single center were reviewed. Patients received a median of two cycles of bortezomib as the retreatment and the overall response rate was 90%. Six (30%), eight (40%) and four (20%) patients achieved a complete response (CR), a very good partial response and a partial response, respectively. Of the 10 patients who had achieved a CR during the initial VTD treatment, six experienced a repeat CR during the retreatment. The median duration of the response was nine months and the median time to progression was 10.5 months. The most common grade I and II adverse events were thrombocytopenia and neutropenia. The short-course bortezomib-based retreatment was well tolerated and the favorable response rates observed suggest that it may be an effective and convenient treatment option for certain patients, particularly elderly patients.

The purpose of this meta-analysis is to determine the incidence of new clinically significant alloantibody formation for multiple myeloma patients that are on daratumumab.

Clonal proliferation of plasma cells within the bone marrow (BM) affects local cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and fatality in multiple myeloma (MM). Consequently, there is an urgent need to find better mechanisms of inhibiting MM growth and osteolytic lesion development. To meet this need and accelerate clinical translation, better models of MM within the BM are required. We developed a clinically-relevant, 3D myeloma BM co-culture model that mimics bone cell-cancer cell interactions within the bone microenvironment. The co-culture model and clinical samples were utilized to investigate myeloma growth, osteogenesis inhibition, and myelomainduced abnormalities in MM-MSCs. This platform demonstrated myeloma support of capillary-like assembly of endothelial cells and cell adhesion mediated-drug resistance (CAM-DR). Also, distinct normal donor (ND)- and MM-MSC miRNA signatures were identified and used to uncover osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D platform provides a simple, clinically-relevant tool to model cancer growth within the bone, useful for investigating skeletal cancer biology, screening compounds, and exploring osteogenesis. Our identification and efficacy validation of novel, bone anabolic miRs in MM opens the floodgate for novel approaches to cancer.

Ark-sey and O’Malley framework used for the proposed scoping review: identifying the research question, identifying relevant studies, study selection, charting the data, collating, summarizing, reporting results, and conducting consultation. We used this framework to obtain a wider view of burden and challenges faced by caregivers of multiple myeloma patient’s researcher will include all original papers, grey literature including unpublished literature. We reported our findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR).

Ark-sey and O’Malley framework used for the proposed scoping review: identifying the research question, identifying relevant studies, study selection, charting the data, collating, summarizing, reporting results, and conducting consultation. We used this framework to obtain a wider view of burden and challenges faced by caregivers of multiple myeloma patient’s researcher will include all original papers, grey literature including unpublished literature. We reported our findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR).

This article is from PLoS ONE , volume 9 . Abstract Cell lines represent the everyday workhorses for in vitro research on multiple myeloma (MM) and are regularly employed in all aspects of molecular and pharmacological investigations. Although loss-of-function studies using RNA interference in MM cell lines depend on successful knockdown, no well-established and widely applied protocol for efficient transient transfection has so far emerged. Here, we provide an appraisal of electroporation as a means to introduce either short-hairpin RNA expression vectors or synthesised siRNAs into MM cells. We found that electroporation using siRNAs was much more efficient than previously anticipated on the basis of transfection efficiencies deduced from EGFP-expression off protein expression vectors. Such knowledge can even confidently be exploited in “hard-to-transfect” MM cell lines to generate large numbers of transient knockdown phenotype MM cells. In addition, special attention was given to developing a protocol that provides easy implementation, good reproducibility and manageable experimental costs.

This article is from Contemporary Oncology , volume 17 . Abstract Neurotoxicity towards the peripheral nervous system which appears clinically in the form of painful neuropathy is an essential dose-limiting factor during the treatment of multiple myeloma. In this review article different forms of this painful neuropathy are presented together with currently available diagnostic tools which are usually applied to confirm the diagnosis. Also, the most often used neurological scales estimating neurological deficit are presented. Special attention is paid to the management of the reversibility of bortezomib-induced neuropathic pain.

Systematic review of all Randomized Controlled trials for Multiple Myeloma to collate the main endpoints utilized.

Melphalan (L-PAM) has been an integral part of multiple myeloma (MM) treatment as a conditioning regimen before stem cell transplant (SCT). After initial response, most treated patients experience relapse with an aggressive phenotype. Increased glutathione (GSH) in MM may mediate resistance to L-PAM. We demonstrated that the GSH synthesis inhibitor buthionine sulfoximine (BSO) synergistically enhanced L-PAM activity (inducing 2–4 logs of cell kill) against nine MM cell lines (also in the presence of marrow stroma or cytokines) and in seven primary MM samples (combination indices

MP (melphalan and prednisolone) plus thalidomide/lenalidomide, MP plus bortezomib, and lenalidomide/thalidomide plus dexamethasone are used regimens for elderly refractory/relapsed multiple myeloma (R/R MM) patients. However, few clinical trials have compared different regimens directly. Therefore, we conducted a network meta-analysis to provide the evidence of efficacy of different regimens in geriatric patients with R/R MM.

MP (melphalan and prednisolone) plus thalidomide/lenalidomide, MP plus bortezomib, and lenalidomide/thalidomide plus dexamethasone are used regimens for elderly refractory/relapsed multiple myeloma (R/R MM) patients. However, few clinical trials have compared different regimens directly. Therefore, we conducted a network meta-analysis to provide the evidence of efficacy of different regimens in geriatric patients with R/R MM.

Introduction: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow. Incidence of MM is increasing rapidly in Asian countries. In a developing country like India diagnosis, risk stratification and access to novel treatment is still a major hurdle Objective: To study the clinico-pathological features of newly diagnosed multiple myeloma patients. Methods: This was a cross sectional hospital based retrospective study conducted in a hospital in eastern India. During the four years of study, 74 cases of multiple myeloma were diagnosed on the basis of International Myeloma Working Group: Criteria for the classification of multiple myeloma and related disorders. The clinical and laboratory characteristics of newly diagnosed patients were studied. Results: Out of the 74 patients, 69% were men and 31% were women. Median age at diagnosis was 55 years (range: 32-81 years). The commonest symptoms observed were fatigue and bone pain. Anemia was present initially in 81% of patients, hypercalcemia in 31.4%, and a serum creatinine level of 2 mg/dL or more in 24.6% patients. The most common monoclonal gammopathy was IgG kappa (44%). Diffuse pattern of bone marrow infiltration, the most common pattern observed in 59% patients. Conclusion: MM patients had male preponderance. Median age of patients was lower compared to western countries with higher percentage of patients with age less than 40 years. Quality of life in MM patients can be improved significantly if there is access to early diagnosis, risk stratification and novel treatment.

Multiple myeloma, a type of plasma cell cancer, is associated with many health challenges, including damage to the kidney by tubulointerstitial fibrosis. We develop an ordinary differential equation (ODE) model which captures the qualitative behavior of the cell populations involved. Specifically, we model the interaction between cells in the proximal tubule of the kidney and free light chains produced by the myeloma monoclonal protein.

February 14, 2014 Town of Bennington proclaims March as Multiple Myeloma Awareness Month. Jan Martin Bopp Produced by Ryan J. Scutt Scuttle Productions

This article is from SpringerPlus , volume 2 . Abstract Objective: The situation of patients with multiple myeloma, whose treatment often implies high-dose chemotherapy and stem cell transplantation that can be associated with severe symptoms and psychological distress, has gained attention in recent psychooncological research. This study followed an idiographic approach in order to identify the areas of life most relevant for the interviewed myeloma patients’ quality of life (QoL) as well as their current satisfaction with these. Methods: 64 patients took part in semi-structured interviews according to the SEIQoL-DW Manual (Schedule for the Evaluation of Individual Quality of Life – Direct Weighting). Visual analogue scales (VAS) were used to gain additional information about a general assessment of the present QoL. Qualitative data evaluation preceded quantitative processing. Groups were compared according to the time elapsed since diagnosis regarding specified areas of life, satisfaction with these and their relative weighting. SEIQoL-DW-indices were correlated to the VAS to reflect on an interindividually comparable parameter. Results: Personal social relationships were mentioned significantly more often as important for QoL than health-related aspects, and in direct comparison were weighted significantly stronger. Regarding the change of areas relevant for QoL over the time elapsed since diagnosis, there was a significant difference between groups concerning the area of spirituality. Satisfaction differed significantly between groups for the field of leisure. Conclusion: The results for the interviewed patients with multiple myeloma point out the need to take into account the importance of social and individual aspects when reflecting on QoL. Similar findings have been reported for different samples. The relevance of an individualized approach is illustrated by the fact that individually named areas of life were rated comparatively strongly in their importance for the patients’ QoL. An overall assessment for the current QoL by means of VAS is regarded as an adequate supplement to the SEIQoL-Profile and an alternative to the SEIQoL-DW-Index.

This article is from Experimental and Therapeutic Medicine , volume 6 . Abstract In this study, the case of a 60-year-old female patient who presented with a subcutaneous mass in the lower right limb is described. The mass was confirmed as a plasmacytoma. The patient was diagnosed with multiple myeloma (MM) λ type stage III international stage system (ISS) and received three cycles of a therapeutic PDT regimen (bortezomib, dexamethasone and thalidomide) and complete remission was achieved. Following a further two cycles of the PDT regimen, the patient proceeded to received a high-dose cyclophosphamide regimen combined with granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization. Fourteen months later, the patient received a high-dose therapy supported by autologous stem cell transplantation (auto-SCT). After six months, a subcutaneous mass was identified in the left side of the patient’s neck and the mass gradually increased in size. The patient exhibited exophthalmos and loss of sight one month later. The masses in the neck and right eyelid of the patient were diagnosed as plasmacytomas. These results, combined with the results of bone marrow (BM) aspiration and protein electrophoresis with immunofixation electrophoresis revealed that the disease had relapsed. The patient received two cycles of a therapeutic CPADT regimen (cyclophosphamide, bortezomib, pharmorubicin, dexamethasone and thalidomide). The patient subsequently achieved complete remission again. The patient refused to continue receiving bortezomib and pharmorubicin for therapy and instead received four cycles of the therapeutic CTD regimen (cyclophosphamide, dexamethasone and thalidomide). Subsequently the patient received local radiotherapy for the masses in the eyes and neck. The patient remained stable after treatment following the initial relapse with a progression-free survival (PFS) time of eight months.

This article is from Journal for Immunotherapy of Cancer , volume 1 . Abstract None

This article is from Oncology Reports , volume 27 . Abstract Camptothecin (CPT) exhibits very strong antitumor effects by inhibiting the activity of DNA topoisomerase I, but its application is greatly limited due to its low solubility and the instability of the active lactone form. To overcome these shortcomings, in the present study, we prepared novel camptothecin nanocolloids based on N,N,N-trimethyl chitosan (CPT-TMC) to efficiently and safely administer CPT systemically. Herein, we investigated the antitumor activity of CPT-TMC against a murine Balb/c myeloma model. Our results showed that CPT-TMC more effectively inhibited tumor growth and prolonged survival time than CPT in vivo, but no statistical difference was observed in vitro between CPT-TMC and CPT. These findings suggest that N,N,N-trimethyl chitosan could increase the stability and the antitumor effect of CPT and CPT-TMC is a potential approach for the effective treatment of multiple myeloma.

This article is from British Journal of Cancer , volume 108 . Abstract Background:: Dichloroacetate (DCA), through the inhibition of aerobic glycolysis (the ‘Warburg effect') and promotion of pyruvate oxidation, induces growth reduction in many tumours and is now undergoing several clinical trials. If aerobic glycolysis is active in multiple myeloma (MM) cells, it can be potentially targeted by DCA to induce myeloma growth inhibition. Methods:: Representative multiple myeloma cell lines and a myeloma-bearing mice were treated with DCA, alone and in combination with bortezomib. Results:: We found that aerobic glycolysis occurs in approximately half of MM cell lines examined, producing on average 1.86-fold more lactate than phorbol myristate acetate stimulated-peripheral blood mononuclear cells and is associated with low-oxidative capacity. Lower doses of DCA (5–10 mℳ) suppressed aerobic glycolysis and improved cellular respiration that was associated with activation of the pyruvate dehydrogenase complex. Higher doses of DCA (10–25 mℳ) induced superoxide production, apoptosis, suppressed proliferation with a G0/1 and G2M phase arrest in MM cell lines. In addition, DCA increased MM cell line sensitivity to bortezomib, and combinatorial treatment of both agents improved the survival of myeloma-bearing mice. Conclusion:: Myeloma cells display aerobic glycolysis and DCA may complement clinically used MM therapies to inhibit disease progression.

This article is from Oncology Letters , volume 6 . Abstract The aim of the present study was to investigate whether asiatic acid (AA), a pentacyclic triterpene derived from Centella asiatica, exerts anti-proliferative effects on multiple myeloma RPMI 8226 cells and to determine the molecular mechanism underlying the anticancer action of AA. The study sought to analyze the potential role of AA on the proliferation of the RPMI 8226 cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium assay. Cell cycle arrest was detected by flow cytometry, and the expression levels of focal adhesion kinase (FAK) in the myeloma cells induced by AA were analyzed using the western blotting and immunoprecipitation methods. The results indicated that AA significantly inhibited cell proliferation in a time- and dose-dependent manner and led to G2/M phase arrest at concentrations of 35 and 40 μmol/l in the RPMI 8226 cells. The expression levels of FAK and p-FAK were distinctly decreased following AA treatment (at the concentration of 40 μmol/l) for 24 h compared with that of the control groups. Taken together, these results demonstrated that AA was able to regulate cell cycle progression in RPMI 8226 cells, thereby significantly inhibiting cell growth. Furthermore, AA decreased the expression levels of FAK, indicating that the antitumor mechanism of AA may be associated with the inhibition of signal transduction mediated by FAK.

This article is from PLoS ONE , volume 9 . Abstract Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic strategies are urgently awaited. A rising body of evidence supports the notion that microRNAs (miRNAs), master regulators of eukaryotic gene expression, may exert anti-MM activity. Here, we evaluated the activity of synthetic miR-34a in MM cells. We found that transfection of miR-34a mimics in MM cells induces a significant change of gene expression with relevant effects on multiple signal transduction pathways. We detected early inactivation of pro-survival and proliferative kinases Erk-2 and Akt followed at later time points by caspase-6 and -3 activation and apoptosis induction. To improve the in vivo delivery, we encapsulated miR-34a mimics in stable nucleic acid lipid particles (SNALPs). We found that SNALPs miR-34a were highly efficient in vitro in inhibiting growth of MM cells. Then, we investigated the activity of the SNALPs miR-34a against MM xenografts in SCID mice. We observed significant tumor growth inhibition (p

This article is from Journal of Hematology & Oncology , volume 7 . Abstract Background: This single-arm study evaluated feasibility, safety, and initial efficacy of electroacupuncture for thalidomide/bortezomib-induced peripheral neuropathy (PN) in cancer patients with multiple myeloma. Methods: Patients with neuropathy ≥ grade 2 received 20 acupuncture treatments over 9 weeks. Results: For the 19 evaluable patients, Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity (FACT/GOG/NTX) mean (SD) scores improved significantly between baseline and week 13 (20.8 [9.6] vs 13.2 [8.5], p = 0.0002). Moderate effect size differences began on week 4, with the largest effect size differences found at week 9 for FACT/GOG/NTX scores, worst pain in the last 24 hours, and pain severity (Cohen’s d = 1.43, 1.19, and 1.08, respectively) and continuing through week 13 (Cohen’s d = 0.86, 0.88, and 0.90, respectively). From baseline to week 13, additional significant improvements were seen as follows: postural stability (1.0 [0.6] vs 0.8 [0.4], p = 0.02); coin test (10.0 [7.4] vs 5.6 [1.9], p 

This article is from BMC Cancer , volume 14 . Abstract Background: Bortezomib offers a novel approach to the treatment of multiple myeloma producing rapid control. The aim of this study was to investigate the outcomes of bortezomib and dexamethasone-treated patients with multiple myeloma. Methods: We conducted a retrospective study of 44 consecutively-treated multiple myeloma patients with bortezomib (1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle or 1.3 mg/m2 intravenously 1, 8, 15, and 22 of every 35-day cycle) and dexamethasone. Results: The median time to progression, progression free survival time, and overall survival time in the treatment groups was 14.9, 14.9, and 38.3 months, respectively. The present study also suggests the possibility that the prognosis of patients with high levels of AST and LDH might be worse. Conclusions: Our results indicate that the treatment of multiple myeloma with bortezomib and dexamethasone is feasible.

This article is from SpringerPlus , volume 3 . Abstract Bisphosphonates (BPs), potent inhibitors of osteoclast-mediated bone resorption, play a major role in the management of patients with multiple myeloma (MM). However, in the case of dental infections, they can lead to bisphosphonate related osteonecrosis of the jaw (BRONJ). This process can be worsened by concomitant antineoplastic therapy. Herein, we present a case of a life-threatening necrotizing fasciitis (NF) as a rare and severe complication of BRONJ after three cycles of lenalidomide and dexamethasone in an MM patient treated with corticosteroid therapy and Ibandronate for 5 years. The patient presented swelling on the right part of the neck, difficulty in swallowing and acute pain, so a magnetic resonance of the head and neck region was performed. It revealed the presence of an NF with a massive extension. Due to the large necrotic area and a rapid progression of the infection, the necrotic tissue had to be removed surgically. Furthermore, a specific antimicrobial treatment as well as 12 sessions of hyperbaric oxygen therapy were needed to cure the patient.Herein, we highlight the potential serious adverse events associated with the use of bisphosphonates and antiangiogenetic drugs in patients with MM. Future studies are needed to evaluate the potential synergistic effects of BPs, corticosteroids and antiangiogenetic drugs.

This article is from British Journal of Cancer , volume 107 . Abstract Background:: The importance of telomerase in multiple myeloma (MM) is well established; however, its response to bortezomib has not been addressed. Methods:: The effect of bortezomib on telomerase activity and cell proliferation was evaluated in four MM cell lines and in myeloma cells obtained from eight patients. The mechanism of telomerase regulation on epigenetic, transcriptional, and post-translational levels was further assessed in two selected cell lines: ARP-1 and CAG. Clinical data were correlated with the laboratory findings. Results:: Bortezomib downregulated telomerase activity and decreased proliferation in all cell lines and cells obtained from patients, albeit in two different patterns of kinetics. ARP-1 cells demonstrated higher and earlier sensitivity than CAG cells due to differential phosphorylation of hTERT by PKCα. Methylation of hTERT promoter was not affected. Transcription of hTERT was similarly inhibited in both lines by decreased binding of SP-1 and not of C-Myc and NFκB. The ex vivo results confirmed the in vitro findings and suggested existence of clinical relevance. Conclusion:: Bortezomib downregulates telomerase activity in MM cells both transcriptionally and post-translationally. MM cells, both in vitro and in patients, exhibit different sensitivity to the drug due to different post-translational response. The effect of bortezomib on telomerase activity may correlate with resistance to bortezomib in patients, suggesting its potential utility as a pre-treatment assessment.

This article is from International Journal of Biomedical Science : IJBS , volume 2 . Abstract A 71-year-old Chinese male was referred for severe dry eyes who suffered from multiple corneal melting ulcers and underwent a long-term and high-dosage interferon alpha-2b (INFα-2b) treatment for multiple myeloma (MM). The patient was diagnosed to have MM 12 years ago, and since then INFα-2b (3-million units, intramuscularly, three times a week) was prescribed until the present. Two years ago, diffuse superficial punctuate epithelial defects, filaments and multiple melting ulcers in his cornea were noted. Sjögren’s syndrome was diagnosed after the salivary gland biopsy. In addition to preservative-free topical lubricants, bilateral permanent punctal occlusion and tarsorraphy were performed but in vain. Topical and systemic immunosuppressants including corticosteroids, cyclosporin and methotrexate improved his corneal condition successfully. The present case suggests a relationship between INFα-2b and Sjögren’s syndrome. Long-term use of INFα-2b may impair tear functions and complicate corneal melting ulcers. Immunosuppressants play a role in treatment of INFα-2b associated keratopathy.

Multiple Myeloma

Introduction: Serum immunofixation electrophoresis (sIFE) and serum free light chains (sFLC) immunoassays are fundamental for serum monoclonal protein diagnosis and monitoring. In this study, we compared the ability of these assays to detect monoclonal proteins in stem cell transplanted patients. Methods: Three hundred sixty sera belonging to 145 patients affected by MM after autologous stem cell transplantation [113 intact immunoglobulin multiple myeloma (IIMM) and 32 free light chains multiple myeloma (LCMM)] were analyzed by both sIFE and sFLC assay, respectively performed with the Binding Site Minifix Kit and the Binding Site Freelite kit on Cobas-Integra 400 Plus (Roche). Results: Two hundred one samples (55.8%) had an abnormal κ/λ ratio and 32.7% had a monoclonal restricted band in sIFE. For 61.38% samples, there was a concordance between sIFE and sFLC and there wasn’t for 139 samples (p<0.0001). Kappa Cohen’s coefficient was weak (κ= 0.25). When compared to sFLC immunoassay for IIMM, sIFE demonstrated a weak sensitivity of 80.7%, which increases to 94.74% when we compared only LCMM results. Accuracy of sIFE respect to sFLC was the better for IIMM (70.7%), than for all type MM (61.4%), and there was a significant difference between the accuracy of either of these techniques, when performed singly for all MM type, IIMM and LCMM. Conclusion: sFLC assay role in IIMM monitoring is to be confirmed by further studies. sFLC assay is a sensitive tool for the monitoring of patients after transplantation, and that it may be associated to sIFE assay to better individualizing minimal residual disease.

This article is from The Pan African Medical Journal , volume 16 . Abstract Multiple myeloma is a malignant plasma cell disorder occurring mostly in people above 60 years old. The authors describe a case of multiple myeloma in a 36-year-old patient revealed by spinal cord compression and Herpes zoster with a rapidly unfavourable outcome.

This article is from Asian Spine Journal , volume 8 . Abstract Study Design: Retrospective comparative study and technical note. Purpose: To determine if there is a difference in clinical and radiographic parameters between unilateral and bilateral kyphoplasty in a uniform cancer population and to stress the importance of preoperative planning. Overview of Literature: While unipedicular kyphoplasty is gaining popularity, a few comparative studies have reported on superior kyphotic reduction with the bipedicular approach. Methods: We reviewed 69 myeloma patients with 105 operated levels (51 levels were done bilaterally vs. 54 unilaterally). Pain reduction, height restoration, cement volume and complications were recorded up to three months postoperatively. A technical note to identify the skin entry point on the basis of the magnetic resonance imaging and fluoroscopy (lateral view) is being described. Results: Both procedures resulted in significant pain reduction (5.4-5.6/10 points, p=0.8). There was significant height restoration after the operation (p

This article is from GMS German Medical Science , volume 9 . Abstract Purpose: Introduction of lenalidomide has expanded the therapeutic options for refractory and recurrent multiple myeloma (MM) patients. However, the application of the approved doses may be difficult in some patients due to adverse effects. Experimental design: Therefore, we evaluated the efficacy and safety of lenalidomide in 10 patients with relapsed and refractory MM who received a reduced dose due to leukopenia (4), polyneuropathy (1), muscle cramps (1), thrombocytopenia (1), renal insufficiency (1), at the request of patient (1), as continuous therapy (1), either from the beginning (2) or during treatment (8). They received lenalidomide at a mean (median) daily dose of 14 (15) mg/d once a day (days 1–21 every 28 days) in combination with dexamethasone at a mean (median) dose of 17.6 (28) mg per day (4–40 mg) on days 1–4, 9–12 and 17–20. Results: Mean (median) duration of treatment with lenalidomide was 15.1 (15) months. Partial response or better was reported in seven and minimal response or better was reported in eight patients. Mean (median) values for time-to-progression (TTP) and for progression-free survival (PFS) were 8.7 (4) months. Mean overall survival (OS) has not been reached, all patients are still alive. Conclusion: In conclusion, dose-reduced lenalidomide is an effective and well tolerated treatment for patients with recurrent or refractory MM who cannot tolerate full doses.

This article is from Cell Death & Disease , volume 2 . Abstract The huge majority of myeloma cell lines express TNFR2 while a substantial subset of them failed to show TNFR1 expression. Stimulation of TNFR1 in the TNFR1-expressing subset of MM cell lines had no or only a very mild effect on cellular viability. Surprisingly, however, TNF stimulation enhanced cell death induction by CD95L and attenuated the apoptotic effect of TRAIL. The contrasting regulation of TRAIL- and CD95L-induced cell death by TNF could be traced back to the concomitant NFκB-mediated upregulation of CD95 and the antiapoptotic FLIP protein. It appeared that CD95 induction, due to its strength, overcompensated a rather moderate upregulation of FLIP so that the net effect of TNF-induced NFκB activation in the context of CD95 signaling is pro-apoptotic. TRAIL-induced cell death, however, was antagonized in response to TNF because in this context only the induction of FLIP is relevant. Stimulation of TNFR2 in myeloma cells leads to TRAF2 depletion. In line with this, we observed cell death induction in TNFR1-TNFR2-costimulated JJN3 cells. Our studies revealed that the TNF-TNF receptor system adjusts the responsiveness of the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms that generate a highly context-dependent net effect on myeloma cell survival.

This article is from Cell Journal (Yakhteh) , volume 15 . Abstract Objective:: Multiple myeloma (MM) is a plasma cell malignancy where plasma cells are increased in the bone marrow (BM) and usually do not enter peripheral blood, but produce harmful factors creating problems in these patients (e.g. malignant plasma cells over activate osteoclasts and inhibit osteoblasts with factors like RANKL and DKK). These factors are a main cause of bone lesion in MM patients. Recently SOST gene which responsible to encodes the sclerostin protein was identify. This protein specifically inhibits Wnt signaling in osteoblasts (inhibition of osteoblast differentiation and proliferation) and decrease bone formation and can also cause bone lesion in MM patients. Materials and Methods:: In this experimental study, human myeloma cell lines (U266 b1) were purchased from Pasteur Institute of Iran. Samples consisted of BM aspirates from the iliac crest of MM patients. BM with more than 70% plasma cell were selected for our study (6 patients) and one healthy donor. RNA extraction was done with Qiagen kit. was undertaken on mRNA of samples and cell lines. Also we purchased unrestricted somatic stem cells from Bonyakhte Company to evaluate the effect of soluble factors from myeloma cell lines on osteogenic differentiation medium. Results:: Our results showed that SOST is expressed significantly in primary myeloma cells derived from MM patients and myeloma cell lines. In other words, patients with more bone problems, express SOST in their plasma cells at a higher level. In addition, myeloma cells inhibit osteoblast differentiation in progenitor cells from umbilical cord blood stem cell (UCSC) in osteogenic inducing medium. Conclusion:: There are many osteoblast maturation inhibitory factors such as DKK, Sfrp and Sclerostin that inhibit maturation of osteoblast in bone. Among osteoblast inhibitory agents (DKK, Sfrp, Sclerostin) sclerostin has the highest specificity and therefore will have less side effect versus non-specific inhibitory agents. Our results also show that based on SOST expression in MM, there is a potential to inhibit sclerostin with antibody or alternative methods and prevent bone lesion in MM patients with the least side effect.

This article is from Experimental and Therapeutic Medicine , volume 6 . Abstract The present study aimed to evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the response and outcome of patients with multiple myeloma (MM) and to analyze the factors influencing the prognosis of the disease. Retrospective analysis was performed in 27 patients with MM who had been treated by ASCT (ASCT group) and 28 patients treated with combined chemotherapy only (non-ASCT group) from May 2004 to August 2011. The impact on the depth of response, progression-free survival (PFS) and overall survival (OS) times, as well as associated prognostic factors of patients with MM, were analyzed. All patients successfully underwent hematopoietic reconstruction without transplantation-related mortality. The complete remission (CR) rate of patients in the ASCT group significantly increased from 25.9% (7/27) before ASCT to 70.4% (19/27) following ASCT (P 0.05). Univariate analysis in the ASCT group demonstrated that maintenance and consolidation therapies were associated with significant increases in PFS (P=0.01) and OS (P

This article is from Blood Cancer Journal , volume 1 . Abstract Comorbidities have been demonstrated to affect progression-free survival (PFS) and overall survival (OS), although their impact in multiple myeloma (MM) patients is as yet unsettled. We (1) assessed various comorbidities, (2) compared established comorbidity indices (CIs; Charlson comorbidity index (CCI), hematopoietic cell transplantation-specific comorbidity index (HCT-CI)), Kaplan Feinstein (KF) and Satariano index (SI) and (3) developed a MM-CI (Freiburger comorbidity index, FCI) in 127 MM patients. Univariate analysis determined moderate or severe pulmonary disease (hazard ratio (HR): 3.5, P

This article is from Journal of the Korean Association of Oral and Maxillofacial Surgeons , volume 39 . Abstract Multiple myeloma (MM) is a disease reported to account for 1% of all cancers and 10% of hematological malignant diseases. Unlike other malignant diseases that are transferred to the osseous tissues, MM does not show new bone formation, is associated with characteristic osteolytic lesions, and shows monoclonal protein (M-protein) on the immunohematological test, which is an important index in its diagnosis. Solitary lesions of MM are rare in the head and neck area, and, in most cases, MM of the head and neck area is related to systemic sympomts.

This article is from Clinical Pharmacology : Advances and Applications , volume 6 . Abstract Carfilzomib, a selective proteasome inhibitor approved in the USA in 2012, is a single agent for relapsed and refractory multiple myeloma. Carfilzomib is administered as a 2–10-minute infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle at a starting dose of 20 mg/m2 for cycle 1 and a target dose of 27 mg/m2 thereafter. In the pivotal Phase II study (PX-171-003-A1), carfilzomib 20/27 mg/m2 provided durable responses in a heavily pretreated population with relapsed and refractory multiple myeloma (n=266), with an overall response rate of 22.9% and a median duration of response of 7.8 months. In an integrated safety analysis of four Phase II studies, common adverse events (32.7%–55.5%) included fatigue, anemia, nausea, thrombocytopenia, dyspnea, and diarrhea. Grade 3/4 adverse events were generally hematologic and included thrombocytopenia (23.4%), anemia (22.4%), and lymphopenia (18.1%). Serious adverse events included pneumonia (9.9%), acute renal failure (4.2%), pyrexia (3.4%), and congestive heart failure (3.4%). New or worsening peripheral neuropathy was infrequent (13.9% overall, 1.3% grade 3, no grade 4). This review discusses findings of the integrated safety analysis and provides practical experience from a single institution in managing treatment-related and disease-related adverse events. Individualized treatment with proactive management of side effects and complications allows patients with advanced multiple myeloma to remain on carfilzomib for extended periods.

This article is from BMC Genomics , volume 14 . Abstract Background: Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. Results: We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Conclusions: Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver genes in cancer genomics studies. The accompanying R code is available at http://www.canevolve.org/dosageEffect/.

This article is from Oncology Letters , volume 8 . Abstract High frequencies of inherited variants in the Mediterranean fever (MEFV) gene have been identified in patients with multiple myeloma (MM). The sample size of the present pilot study was small, therefore, the actual frequency of inherited variants in the MEFV gene could be investigated in patients with MM. Twenty-eight patients with MM and 65 healthy controls were included in the study. Six heterozygous and one homozygous (E148Q/E148Q) variant was identified in patients with MM. None of the patients had a family history compatible with familial Mediterranean fever. In the healthy control group, 11 heterozygous variants were identified. The difference in the overall frequency of the inherited variants in the MEFV gene between the MM patients and the controls was statistically significant (χ2=4.905; P=0.027). In conclusion, a high frequency of inherited variants in the MEFV gene was identified in patients with MM. Based on the current data, it is hypothesized that the MEFV gene is a cancer susceptibility gene. Additional evidence, such as familial aggregation, monozygotic versus dizygotic twin concordance, and tumors in genetically engineered model organisms, is required in order to support this hypothesis.

Recent advances in treating newly diagnosed multiple myeloma (NDMM) have explored the addition of anti-cd38 antibodies to established three-drug regimens, forming quadruplets. This systematic-review and meta-analysis seeks to support clinicians in evaluating treatment options by providing insights into the potential benefits and risks of upfront anti-CD38 quadruplet therapies, which may help inform NDMM management.

1Winesburg, Ohio

By Sherwood Anderson

Published in 1919, and listed on the Modern Library roster of the 20th century's 100 greatest novels in English, Winesburg, Ohio presents a series of loosely related character studies of the inhabitants of a fictional Midwestern town that together form a novel of unusual unity and vision. The inarticulate and lonely citizens of Winesburg, each with his or her own secret tale to tell, frequently relate those tales to, or through their interactions with, the character of George Willard, a young Winesburg citizen on the cusp of manhood with dreams of becoming a writer. Thus Winesburg tells the story of the townspeople's loneliness and alienation in parallel with the tale of George's own coming of age. The citizens of Winesburg are described obliquely as "grotesques," but as the introductory chapter makes clear, "The grotesques were not all horrible. Some were amusing, some almost beautiful . . ." (Description by Stewart Wills)

2Seven O'Clock Stories

By Robert Gordon Anderson

"Not once upon a time but just now, in a white house by the side of a road, live three happy children. Their mother and father gave them very odd names, for two old uncles and one aunt, which pleased the old people very much. Their names are all written in the big family Bible,--Jehosophat Green, Marmaduke Green, and Hepzebiah Green." So begins this collection of bedtime stories for children, one each night for twenty days, involving these three happy children and their playmates. (Summary by P. Cunningham)

3Security

By Poul William Anderson

“Security” tells the story of a compartmentalized government physicist ordered by secret police to complete experiments aimed at developing a new weapon. He is brought to a hidden space station and put in charge of the project but there are many questions. In a world of spies watching spies it’s sometimes hard to know what’s patriotic. -- Poul Anderson was a Golden Age Science Fiction and Fantasy author. “Security” first appeared in the magazine “Space Science Fiction” in February of 1953 (Summary by Gregg Margarite)

4Chapter Ends

By Poul William Anderson

Far, far in the future the Earth is still spinning around the Sun, on the edge of the galaxy, dozing in obscurity, forgotten by it's trillions of progeny and completely irrelevant. But this doesn't matter to the few millions who still live there in simplicity and quiet happiness. But then interstellar politics dictates that they must all leave Earth because ... well, listen to the story as told by the great Poul Anderson as he explores what the Earth means to humans and to one man in particular. (Summary by Phil Chenevert)

5Spell of the Hawaiian Islands and the Philippines

By Isabel Anderson

Isabel Anderson has written a most interesting travelogue of Hawaii and The Philippines. Actually it is more of a history lesson. Anyone with any interest whatsoever in the South Pacific will find this book very interesting indeed, to note all that has changed since Mrs. Anderson had traveled there. (Summary by William Tomcho)

Eamont was an opium clipper built in Cowes. It was the subject of an 1891 book, A cruise in an opium clipper, by Captain Lindsay Anderson. Eamont was involved in the opening of Japan to foreigners in 1858, serving as a dispatch boat between Nagasaki and Shanghai, and was one of the first vessels to open up a trade with Formosa…. The Eamont was sent on some very dangerous trips. She was one of the first vessels to open up a trade with Formosa, and made the first survey of the port of Taku, which she entered by bumping over the reef in spite of a tremendous surf beating upon it at the time, a most daring performance. And in her efforts to trade with the Formosans she had to withstand the attack of hundreds of armed natives right on top of a typhoon, which she succeeded in riding out on her moorings. But the captain of the Eamont was a famous fighting man, as the Chinese pirates knew to their cost…. The Eamont was also employed in the negotiations for the first commercial treaty with Japan. (See Wikipedia article on Eamont (schooner)) - Summary by Wikipedia and david wales

Anderson served as third officer aboard the Eamont. Eamont was an opium clipper built in Cowes. Eamont was involved in the opening of Japan to foreigners in 1858, serving as a dispatch boat between Nagasaki and Shanghai, and was one of the first vessels to open up a trade with Formosa. The Eamont was employed in the negotiations for the first commercial treaty with Japan. On this occasion she ran into Nagasaki and quietly dropped anchor, in spite of the fact that opposition to the proposed commercial treaty was very strong at the time. On the following morning 150 boat-loads of Japanese attempted to tow her to sea, being evidently ignorant of an anchor's raison d'etre. But though they attempted several similar methods to get rid of her they refrained from any armed attack, and, eventually, her mission was completely successful. This was in 1858, and the Eamont's crew saw many wonderful sights in that tierra incognita. The September Typhoon of 1858 destroyed several well-known opium clippers at Double Island, including the Anonyma, Gazelle, Pantaloon, and Mazeppa. Eamont was anchored off Double Island, with "150 fathoms of chain out and a second anchor backed on it at 60 fathoms." The waves in the anchorage were estimated to be as large as 40 feet, and the Eamont’s crew had to cut away her masts. Eamont was one of only two ships in that anchorage to survive the night, the other being the Hazard. (See Wikipedia article on Eamont (schooner)) (Wikipedia and david wales)

A Voice from Harper's Ferry is the abolitionist testament of Osborne Perry Anderson, the only surviving black participant in the 1859 raid on Harpers Ferry organized by John Brown. The book details the motivations and preparations for the raid, the events that unfolded over several days in October 1859, and Anderson's subsequent escape. It ends with a short selection of poems from various sources honoring Brown and the movement for abolition. (summary by JR Martin)

9Sentiment, Inc.

By Poul William Anderson

The way we feel about another person, or about objects, is often bound up in associations that have no direct connection with the person or object at all. Often, what we call a "change of heart" comes about sheerly from a change in the many associations which make up our present viewpoint. Now, suppose that these associations could be altered artificially, at the option of the person who was in charge of the process.... (from the Blurb)

“The Triumph of the Egg” is a collection of stories and poems by Sherwood Anderson. Abandoning the interconnected quality of his more famous “Winesburg, Ohio,” the author adopts a variety of perspectives and settings while exploring similar themes: personal growth, disillusionment, loneliness, and urban-rural contrast. In the North American Review, critic Lawrence Gilman wrote, “Mr. Anderson has achieved a beauty that irradiates his page.” Though largely overshadowed by that celebrated, earlier book, “The Triumph of the Egg” remains a foundational work for Modernist literature, proven by its winning the first annual Dial Award from the influential journal The Dial.<br /><br /> NOTE TO LISTENERS: The second story in this collection, “I Want to Know Why,” contains language that may be offensive.<br /> (summary by Ben Adams)

11How to Do Chemical Tricks

By A. T. Anderson

While a bit outdated in many of the more complex descriptions of several of the phenomena described, this book is nonetheless still fun and relevant for a person interested in basic chemistry or physics tricks, and the devices built in the book can be easily replicated with more modern materials. The book is split up into many little experiments, tricks, with an explanation on how it works, what's happening, and how to reproduce the effects at home.(summary by Kyle Van DeGlast)

12American Big-Game Hunting

By George S. Anderson, Winthrop Chanler, Oscar F. C. Crocker, Walter Bourchier Devereux, George Bird Grinnell, Arnold Hague, W. D. Pickett, Archibald Rogers, Theodore Roosevelt, Bronson Rumsey, Dean Sage, Roger D. Williams and Owen Wister

The first book published by The Boone and Crockett Club founded by Theodore Roosevelt and George Grinnell, who declared in their Editors Note: "Hunting big game in the wilderness is, above all things, a sport for a vigorous and masterful people. The rifle-bearing hunter, whether he goes on foot or on horseback, whether he voyages in a canoe or travels with a dog-sled, must be sound of body and firm of mind, and must possess energy, resolution, manliness, self-reliance, and capacity for hardy self-help. In short, the big-game hunter must possess qualities without which no race can do its life-work well; and these are the very qualities which it is the purpose of this Club, so far as may be, to develop and foster."<br /><br /> A bit outdated as to the equipment they used, this book is nevertheless an intense look at the west in early days, and at the beginnings of the conservationist movement in America. Each chapter focuses on a different animal, from buffalo, mountain goat, elk, pronghorn sheep, grizzlies, etc., indigenous peoples, different areas like the Rockies and Yellowstone, and it still captures the essence of the spirit of the hunt.<br /><br /> The book ends with a list of the club's original 100 members, a veritable Who's Who of Generals, Colonels, Doctors, Senators and Representatives, amongst them that most illustrious Gen'l William T. Sherman. ( ~ Michele Fry, read by LibriVox Volunteers)

13Windy McPherson's Son

By Sherwood Anderson

Windy McPherson's Son is the story of Sam McPherson's rise in the world of business and search for emotional enlightenment in later life. McPherson starts out as an ambitious newsboy in Caxton, Ohio, with drunkard of a father who constantly embarrasses him. Eventually, after his mother's death and an episode with a middle-aged schoolteacher, McPherson leaves Caxton for Chicago. In Chicago, he gets a job as a buyer of farm implements and establishes his reputation in business. While his professional life is blossoming, his personal life suffers. After meeting Sue Rainey, the daughter of his boss Colonel Rainey, they get married and twice fail to have children. Following a business deal that forces his father-in-law out of his own company, McPherson and Sue Rainey separate. One day, once McPherson had become quite wealthy, he gets a telegram saying that Colonel Rainey committed suicide. This causes Sam to realize that he is unhappy with his life. This feeling inspires him to leave Chicago and travel all over becoming involved in various adventures. Finally, McPherson's comes across a promiscuous and alcoholic mother of three children. A deal is made and McPherson gets custody of the children. Showing up with the children at Sue's current place of residence, the five of them become family. ( Wikipedia)

14Inside Earth

By Poul William Anderson

This story takes place in the not so distant future. Earth has been conquered and is a subjugated planet, the much too humanoid new rulers now extract heavy taxes, control industry and reproduction and interfere in every aspect of life. Rumors of their brutality and vicious massacres increase every day. Obviously, they must be thrown out and rebellion seethes among the patriots. But on the other hand, others are not so eager to get rid of the overlords: the terrible nationalistic wars have been stopped, famine is long gone and health care is almost universally available. Still, the elite intellectual portion of the earth's population plot to remove the heavy heel of the oppressors from their necks and let earth be free again. But time and again the attempts for freedom have been crushed the Valgolians mainly because national, ethnic, religious and racial prejudices and hatred among the earthlings keep the conspirators from working together. Obviously, no conqueror wants his subjects to revolt against his rule. Obviously? This one would go to any lengths to start a rebellion!

15Sensitive Man

By Poul William Anderson

Poul Anderson delves into the realm of human potential in this exciting story and asks some penetrating questions for us to think about. What if psychology finally enabled people to even partially control all those automatic reactions of our minds and bodies? What if we were not slaves to anger, fear, emotions, hormones, blood pressure and the thousand other things that our bodies 'take care of' from instant to instant? What if those things could be brought under the control even partially of our reason and minds? In this story one man stood between a power-hungry cabal and their world mastery—but a man of, shall we say, unusual talents.

16Hunting In Many Lands

By Henry T. Allen, George S. Anderson, Daniel Moreau Barringer, Winthrop Chanler, George H. Gould, Madison Grant, William Woodville Rockhill, Theodore Roosevelt, Elliott Bulloch Roosevelt, Alden Sampson, Henry L. Stimson, Charles E. Whitehead, Caspar W. Whitney and Roger D. Williams

The first volume published by the Boone and Crockett Club, entitled "American Big Game Hunting," confined itself to sport on the American continent. This second volume presents a number of interesting sketches written by club members who have hunted big game in other lands. Essays include: Hunting in East Africa, To the Gulf of Cortez, A Canadian Moose Hunt, A Hunting Trip in India, Dog Sledging in the North, Wolf-Hunting in Russia, A Bear-Hunt in the Sierras, The Ascent of Chief Mountain, The Cougar, Big Game of Mongolia and Tibet, Hunting in the Cattle Country, Wolf-Coursing, Game Laws, and Protection of the Yellowstone National Park. - Summary by Michele Fry

Margaret Steele Anderson was born in Louisville, Kentucky in 1867 and was educated in the public school of Louisville, with special courses at Wellesley College. From 1901 Miss Anderson was Literary Editor of the `Evening Post' of Louisville, and was known as one of the most discriminating critics of the South. She published only one volume of verse, "The Flame in the Wind", 1914. (David Lawrence

Frederick Irving Anderson was a New York newspaperman who had a second career writing mystery stories for the "slick" magazines such as the Saturday Evening Post. The Infallible Godahl is a collection of some of his first stories. Godahl is a clever gentleman thief, who might be thought of as an American version of Raffles or Arsene Lupin. - Summary by Winston Tharp

Margaret Steele Anderson's tribute to the men left on board the doomed ship, some of whom followed the "Women and children first" tradition of the sea. - Summary by David Lawrence

LibriVox volunteers bring you 18 recordings of Michael Angelo's "Dawn" by Margaret Steele Anderson.<br> This was the Weekly Poetry project for February 10, 2019. <br> ------<br> Dawn is a sculpture by Italian Renaissance artist Michelangelo, executed for the Medici Chapel in the area of the tomb of Lorenzo de' Medici in Florence, Italy.<br> It is part of a second pair (the second being Dusk), which followed Day and Night in his work on the Chapel. - Summary by Wikipedia

21Snowball

By Poul William Anderson

Simon's new source of power promised a new era for Mankind. But what happens to world economy when anyone can manufacture it in the kitchen oven?... Here's one answer! Summary by Realisticspeakers

22Golden Slave

By Poul William Anderson

100 B.C. The Cimbrian hordes galloped across the dawn of history and clashed in screaming battle against the mighty Roman legions. Led by their chief, Boierik, and his son, Eodan, the hungry and homeless pagan tribes hurled back the Romans time after time in their desperate search for land. But for all the burning towns, the new-caught women weeping, the wine drunk, the gold lifted, the Cimbri did not find a home. And now it was over. At Vercellae the Roman armies shattered them completely. Only a few survived—and for them death would have been more merciful. Eodan, the proud young chieftain, had been caught and sold into slavery, his infant son murdered and his beautiful wife, Hwicca, taken as a concubine. But whips and slave chains could not break the spirit of this fiery pagan giant who fought, seduced and connived his way to a perilous freedom to rescue the woman he loved. - Summary by original text

A DOUBTER'S Doubts about Science and Religion was first published anonymously, at a time when the author was Assistant Commissioner of Police and Head of the Criminal Investigation Department, at Scotland Yard (London). As the book is addressed to men of the world, it speaks from the standpoint of scepticism — the true scepticism which tests everything, not the sham sort which credulously accepts anything that seems to discredit the Bible. If, for example, the Bible taught evolution, it may be averred that evolution would be scoffed by many who now cling to it with a childlike faith worthy of the infant class in the Sunday School. With the true sceptic it is merely a philosophic theory. The reader will thus be prepared to find that destructive criticism is in the main the author's method. To some the book will seem unsatisfactory on this account, and yet they must recognise the importance of thus refuting the claims which infidelity makes to superior enlightenment. It may be thought, perhaps, that the criticisms they contain are out of date, now that Spencerism is dead, and Darwinism discredited. But though biological theories which reigned supreme a few years ago have been abandoned or modified by "men of light and leading," their influence still prevails with the general public and in response to appeals from several quarters the chapters in question are here reproduced. - Summary by Preface