Cryptococcal meningoencephalitis in patients with mantle cell lymphoma on ibrutinib

Kai Sun, Saro Kasparian, Swaminathan Iyer and Sai Ravi Pingali

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Case 15-2018: An 83-Year-Old Woman with Nausea, Vomiting, and Confusion

Presentation of Case. Dr. Andrew S. Hoekzema (Medicine): An 83-year-old woman was admitted to this hospital in the winter because of nausea, vomiting, diarrhea, and confusion. One week before admission, rhinorrhea, sore throat, and nonproductive cough developed. The patient felt feverish but did…

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Classic Hodgkin lymphoma involving the endometrium: an extremely rare finding associated with refractory/widespread disease

Abstract

Classic Hodgkin lymphoma (HL) involving the endometrium is extremely rare as lymphoma involving the female genital tract is uncommon in general and those that do are most commonly non-Hodgkin lymphomas. Here, we present a patient with refractory classic HL where PET scan imaging results led to an endometrial biopsy that confirmed uterine involvement of her disease.

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Lymphedema following cancer therapy: overview and options

Abstract

This summit focusing on lymphedema following cancer therapy was held during the 7th International Symposium on Cancer Metastasis through the Lymphovascular System. It was unique for the inclusion of patients with lymphedema joining physicians, therapists, healthcare professionals, and researchers to highlight what is known and more importantly what is unknown about the current state of research and treatment in the United States. The session opened with an introduction to lymphedema and then explored the incidence of multiple cancer-related lymphedemas, imaging tools and techniques useful for the diagnosis of lymphatic system abnormalities, and the new findings concerning the genetics of cancer-related lymphedema. It closed with a review of advocacy for patients and healthcare professionals and both conservative and surgical treatment options, followed by a panel discussion and questions. The session provided important information and updates which will be of value for improving the rehabilitation and overall support of patients with cancer-related lymphedema.

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Zika Virus Baculovirus-Expressed Virus-Like Particles Induce Neutralizing Antibodies in Mice

Abstract

The newly emerged mosquito-borne Zika virus (ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles (VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane (prM) and envelope (E) proteins were co-expressed in insect cells and self-assembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.

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Possible association of CAG repeat polymorphism in KCNN3 encoding the potassium channel SK3 with oxaliplatin-induced neurotoxicity

Abstract

Introduction

Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN.

Materials and methods

We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density. A retrospective study was carried out on patients with colorectal cancer who had received oxaliplatin-based chemotherapy. DNA for KCNN3 genotyping was extracted from leukocytes. The region containing the CAG repeats was amplified by PCR and the products separated by capillary electrophoresis for length analysis. The patients were divided into three groups depending on whether they carried two short alleles, one short allele and one long allele, or two long alleles. The primary endpoint was the onset of grade 2 or 3 neuropathy to oxaliplatin.

Results

There was no difference in current density, but oxaliplatin induced a differential effect on apamin-sensitive current density between the two isoforms expressed in the HEK cell lines. There was a significant reduction of store-operated calcium entry into cells expressing the short and more active isoform only after high concentration of oxaliplatin exposition. Eighty-six patients were included in the clinical study. There was no significant association between OIN and KCNN3 polymorphism for the three groups.

Conclusion

We observed a slight association between OIN and CAG repeat polymorphisms of the KCNN3 gene in a preclinical model, but not a clinical study.

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Cancers, Vol. 10, Pages 144: Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro

Cancers, Vol. 10, Pages 144: Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro

Cancers doi: 10.3390/cancers10050144

Authors: Rodolfo Garza-Morales Roxana Gonzalez-Ramos Akiko Chiba Roberto Montes de Oca-Luna Lacey R. McNally Kelly M. McMasters Jorge G. Gomez-Gutierrez

Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated. Human TNBC MDA-MB-231 and HCC1937 cells and mouse 4T1 cells were infected with an OAd expressing the red fluorescent protein mCherry on the virus capsid (OAdmCherry) alone or in combination with TMZ. TNBC cells treated with OAdmCherry/TMZ displayed greater mCherry and adenovirus (Ad) early region 1A (E1A) expression and enhanced cancer-cell killing compared to OAdmCherry or TMZ alone. The combined therapy-mediated cell death was associated with virus replication and accumulation of the autophagy marker light chain 3 (LC3)-II. Overall, this study provides experimental evidence of TMZ’s ability to increase oncolytic virotherapy in both human and murine TNBC cells.

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