Risk Factors for Eribulin-induced Severe Neutropenia in Patients With Recurrent Breast Cancer.

BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for advanced and metastatic breast cancer. However, severe neutropenia occurs in 30-40% of patients and interferes with the recommended treatment schedule. Neutropenia is a major cause of treatment interruptions, delays, or even relative dose reductions. This study aimed to examine the risk factors for severe neutropenia after eribulin treatment. PATIENTS AND METHODS: We retrospectively evaluated 263 patients with metastatic breast cancer who had received eribulin therapy. Risk factors for severe neutropenia in the first cycle were evaluated. RESULTS: Severe neutropenia in cycle 1 occurred in 50% of the patients. Multivariate analysis suggested six risk factors for severe neutropenia: low baseline neutrophil count and body mass index, high aspartate aminotransferase and bilirubin levels, creatinine clearance (CrCl) less than 50 ml/min, and eribulin dose of 1.4 mg/m2 Conclusion: This is one of the few studies to simultaneously examine both hepatic and renal functions in relation to severe neutropenia induced by eribulin. We have provided important information to support the close monitoring of patients with these risk factors and subsequent dosage adjustments, if necessary.

Basic structure and cytocompatibility of giant membrane vesicles derived from paraformaldehyde-exposed human cells.

Exposure of cultured mammalian cells to paraformaldehyde (PFA) is an effective approach to induce membrane blebs, which is followed by their detachment from the cellular cortex to yield giant membrane vesicles in extracellular spaces. Although PFA-induced giant vesicles have attracted significant interest in the field of cell membrane dynamics, their biochemical components and cytocompatibility remain largely unknown. In this report, we exposed human cervical cancer HeLa cells to PFA under metal-free buffer conditions to produce giant vesicles. We analyzed the components and structure of the purified PFA-induced giant vesicles. Co-culturing PFA-induced giant vesicles with exponentially growing HeLa cells resulted in docking of a significant number of the giant vesicles to the cell surface with seemingly no cytotoxicity. Intriguingly, we found that pre-treatment of HeLa cells with peptide-N-glycosidase and neuraminidase was effective in facilitating cellular uptake of constituents residing inside the vesicles. The results revealed further details about the effect of PFA on cell membranes and provide insights for studying the interaction between PFA-induced giant vesicles and cultured cells.

Chemical manipulations to facilitate membrane blebbing and vesicle shedding on the cellular cortex.

OBJECTIVES: Most attention has been focused on physiologically generated membrane blebs on the cellular cortex, whereas artificial membrane blebs induced by chemicals are studied to a lesser extent. RESULTS: We found that exposure of HeLa human cervical cancer cells to paraformaldehyde (PFA), followed by incubation in phosphate-buffered saline (PBS) efficiently induced large membrane blebs on the cellular cortex. Intriguingly, sequential exposure of the PFA-treated cells to PBS containing dimethyl sulfoxide (DMSO) facilitated shedding of the blebs from the cellular cortex, yielding a high quantity of large extracellular vesicles in the supernatant, which was applicable to assess the potentials of compounds and proteins as membrane influencers. Similar effects of PFA and DMSO were detected on the cellular cortex of other human, mouse, and fish cells. CONCLUSIONS: Our procedure to facilitate membrane blebbing and vesicle shedding by chemicals may be practical for the manipulation of membrane dynamics and the development of vesicle-inspired technologies using a wide variety of cell types.

Skin Disorders and Primary Tumor Location as Prognostic Factors in Patients with Metastatic Colorectal Cancer Treated with Cetuximab and Chemotherapy

Background: Cetuximab-induced skin disorder is common in colorectal cancer (CRC), and is known to affect prolonged overall survival (OS). Patients with left-sided CRC survive longer than those with right-sided CRC, among those treated with combination cetuximab and chemotherapy. However, no study has evaluated patient prognosis in terms of OS and progression-free survival (PFS) in relation to both tumor location and skin disorder. This study aimed to determine the incidence of skin disorder according to tumor location and analyze the relationship of tumor location and skin disorder with OS. Methods: Patients with metastatic colorectal cancer (mCRC) treated with standard chemotherapy and cetuximab as first-line therapy were included. Differences in the incidence of skin disorders due to the location of the primary tumors were compared in the same patient. The OS and PFS in relation to the location of the primary tumors and presence or absence of skin disorder were also compared. Results: Total frequency of each skin disorder as rash acneiform, paronychia, and dry skin in patients with left- and right-sided mCRC was 70%, 70%, and 43% and 27%, 36%, and 27%, respectively. The median OS was 8.9 months for mCRC on the left-sided without skin disorder and 56.3 months for mCRC on the left-sided with skin disorder. In comparison, the median OS was 10.4 months for mCRC on the right-sided without skin disorder and 11.3 months for mCRC on the right-sided with skin disease (left-sided with skin disorder versus other three group; P<0.001). Conclusions: Primary tumor location and the presence of skin disorder are important factors in patients with mCRC who receive cetuximab. In particular, our results show the new fact that the left-sided and right-sided mCRC survival time were comparable if there is no skin disorder caused by cetuximab.

Successful treatment of meningoencephalitis caused by methicillin-resistant Staphylococcus aureus with intravenous linezolid in an allogeneic cord blood stem cell transplant recipient.

Methicillin-resistant Staphylococcus aureus (MRSA) is an infectious pathogen that commonly occurs after stem cell transplantation. We report a case of meningoencephalitis with multiple abscess formation caused by MRSA, which occurred in a 62-y-old female soon after allogeneic cord blood transplantation, and which was successfully treated by the administration of intravenous linezolid.