[Efficacy of Tapentadol for Neuropathic Pain in Cancer].

Neuropathic pain in patients with cancer often do not respond to both opioid and non-opioid analgesics. Tapentadol has two medical effects: action on the µ opioid receptor and inhibition of noradrenaline reuptake; thus, it is expected to be effective for neuropathic pain. We investigated its effect on neuropathic pain in 40 patients with cancer who received tapentadol between June 2017 and May 2020 at the Japanese Red Cross Nagoya Daini Hospital. We compared the level of neuropathic pain using an NRS before and after tapentadol administration. The NRS score(median)decreased from 7 to 4.5 within 15 days after first administration or dose increase(p<0.05). Twenty-two patients(55%)showed more than 33% improvement in the NRS score. These results suggest that tapentadol may contribute to a reduction in neuropathic pain.

[Necessity of Serum Calcium Concentration Measurement for Investigating Hypocalcemia Induced by Denosumab].

Denosumab is widely used for treating bone metastases in patients with advanced cancer. However, hypocalcemia has been reported as a serious adverse effect during this treatment. Therefore, monitoring serum calcium concentration is essential. During long-term continuous administration ofdenosumab, the burden ofeach blood sampling occasion and medical economics should be clarified; however, the appropriate blood sampling frequency has not yet been confirmed. In the present study, we performed a retrospective investigation of serum calcium concentration after denosumab administration. The results indicated that serum calcium concentration tended to increase with repeated administration. A significant increase was observed at the time ofthe third and sixth administration. This suggested that it was possible to reduce the frequency ofblood sampling during long-term administration ofdenosumab with appropriate calcium supplementation.

[Proactive Efforts by Medical Establishments to Support Working Cancer Patients and Formation of Comprehensive Employment Support Networks in Local Communities].

As part of proactive efforts to support working cancer patients at medical establishments, patients were given advice not to quit working after diagnosis and invited to a cancer counseling and support center. Further, medical treatment plans focusing on treatment period were presented prior to the start of treatment. These plans can be useful for cancer patients who seek support from their employers about changing their working conditions during treatment. Although these active support initiatives for newly diagnosed working cancer patients tended to contribute to a decrease in the rate of early job termination, the number of cancer patients who quit their work did not decrease significantly. There was a limit to work-related support at the clinical site. It is essential for many professionals to collaborate, such as clinicians, occupational health staff and working support professionals in the promotion of measures for balancing work and treatment for cancer patients. In the Tokai area, we set up the Cancer and Employment Workshop in 2015. We have been working to establish a local network to comprehensively support these patients.

Silencing of TBC1D15 promotes RhoA activation and membrane blebbing.

Membrane blebs are round-shaped dynamic membrane protrusions that occur under many physiological conditions. Membrane bleb production is primarily controlled by actin cytoskeletal rearrangements mediated by RhoA. Tre2-Bub2-Cdc16 (TBC) domain-containing proteins are negative regulators of the Rab family of small GTPases and contain a highly conserved TBC domain. In this report, we show that the expression of TBC1D15 is associated with the activity of RhoA and the production of membrane blebs. Depletion of TBC1D15 induced activation of RhoA and membrane blebbing, which was abolished by the addition of an inhibitor for RhoA signaling. In addition, we show that TBC1D15 is required for the accumulation of RhoA at the equatorial cortex for the ingression of the cytokinetic furrow during cytokinesis. Our results demonstrate a novel role for TBC1D15 in the regulation of RhoA during membrane blebbing and cytokinesis.

Effects of 5-mg dose of olanzapine for breakthrough nausea and vomiting in patients receiving carboplatin-based chemotherapy: a prospective trial.

BACKGROUND: Olanzapine 10 mg is recommended for breakthrough chemotherapy-induced nausea and vomiting. However, there is a possibility that 5 mg can be expected to be sufficiently effective. We aimed to investigate the efficacy and safety of olanzapine 5 mg for breakthrough chemotherapy-induced nausea and vomiting. METHODS: A single-arm prospective trial of olanzapine 5 mg every 24 h for 72 h was conducted to treat breakthrough chemotherapy-induced nausea and vomiting in patients receiving carboplatinbased chemotherapy. The primary endpoint was total control (i.e., no emesis, no nausea, and no rescue medications) over 72 h. The secondary endpoints were early efficacy using the nausea scores at 30, 60, and 120 min after taking olanzapine from baseline and adverse events. RESULTS: Among 84 potentially eligible patients, 19 patients who took olanzapine for breakthrough chemotherapy-induced nausea and vomiting were examined. The total control rate was 32% (95% CI: 13- 57%), 65% (95% CI: 38-89%), 65% (95% CI: 38-89%), and 29% (95% CI: 10-56%) during 2-24, 24-48, 48-72 h, and overall period, respectively. The nausea scale significantly reduced after 30 min (P=0.0078), and the scale had been reduced by 67% from the baseline after 60 min. The adverse event of somnolence of any grade was observed in 13 (68%) patients, 6 (32%) of whom had grade 2 and 1 (5%) grade 3 somnolence. CONCLUSIONS: Olanzapine 5 mg did not show the expected effect on the complete disappearance of breakthrough chemotherapy-induced nausea and vomiting within 24 h.

The roles of two distinct regions of PINCH-1 in the regulation of cell attachment and spreading.

Cells attach to the extracellular matrix (ECM) through integrins to form focal adhesion complexes, and this process is followed by the extension of lamellipodia to enable cell spreading. PINCH-1, an adaptor protein essential for the regulation of cell-ECM adhesion, consists of five tandem LIM domains and a small C-terminal region. PINCH-1 is known to interact with integrin-linked kinase (ILK) and Ras suppressor protein 1 (Rsu-1); however, the precise mechanism by which this complex regulates cell-ECM adhesion is not fully understood. We report here that the LIM1 domain of PINCH-1, which associates with ILK to stabilize the expression of this protein, is sufficient for cell attachment but not for cell spreading. In contrast, the C-terminal region of PINCH-1, which binds to Rsu-1, plays a pivotal role in cell spreading but not in cell attachment. We also show that PINCH-1 associates with Rsu-1 to activate Rac1 and that Rac1 activation is necessary for cell spreading. Thus, these data reveal how specific domains of PINCH-1 direct two independent pathways: one utilizing ILK to allow cell attachment, and the other recruiting Rsu-1 to activate Rac1 in order to promote cell spreading.