Ohkawa M, Kamata K, Kawsar SMA, Gerdol M, Fujii Y, et al.
BBA advances •
We here report the novel primary structure of a new member in the galectin family, the β-galactoside-binding lectin HOL-30, from the marine sponge , whose full-length sequence was determined thanks to the combination between Edman degradation and transcriptome analysis. The HOL-30 polypeptide is a tandem-repeat dimeric galectin, consisting of 281 amino acids, which includes two carbohydrate recognition domains (CRDs). Unlike most other galectins described in Porifera, HOL-30 did not have a signal peptide sequence for secretion. In solution, HOL-30 exhibited a molecular weight of 60 kDa, indicating a dimeric organization consisting of two 30 kDa tandem-repeat subunits stabilized by non-covalent interactions. Although the two CRDs had a similar predicted 3D structure, they displayed low pairwise sequence identity, approximately 20 %. HOL-30 exhibited glycan-binding affinities for type-1 (Galβ1-3GlcNAc) and type-2 (Galβ1-4GlcNAc) LacNAc. Furthermore, it also recognized blood type B-oligosaccharides on type-1 and type-2 LacNAc (Galα1-3Gal[Fucα1-2]β1-3/4GlcNAc), and blood type H-oligosaccharide on type-3 (Gal[Fucα1-2]β1-3GalNAcα). The glycan-binding properties of HOL-30 were compared with those of the hRTL galectin, previously identified in , consisting of tetrameric 15 kDa prototype subunits. The two sponge galectins displayed similar, but not identical, carbohydrate-binding properties, as evidenced by the fact that despite effectively binding to vertebrate cultured cells, HOL-30 had minimal impact on cell growth. Antiserum analysis revealed a mosaic distribution of HOL-30 in the parenchymal cells of sponge tissues within dense cell clusters surrounding the spicules.
Horita N, Miyagi E, Mizushima T, Hagihara M, Hata C, et al.
Cancer medicine •
The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66Â years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5Â min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.
Ishibashi K, Aoyama T, Kotaka M, Satake H, Tsuji Y, et al.
Cancer chemotherapy and pharmacology •
The aim of this study was to evaluate the efficacy and safety of first-line chemotherapy with re-introduction of oxaliplatin (OX) more than 6 months after adjuvant chemotherapy including OX. Stage II/III colon cancer patients with neuropathies of grade ≤ 1 who relapsed more than 6 months after adjuvant chemotherapy including OX were considered eligible. Eligible patients were treated with 5-fluorouracil, l-leucovorin and OX plus molecularly targeted agents or capecitabine and OX plus bevacizumab (BV) or S-1 and OX plus BV. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were the overall survival (OS), response rate (RR) and toxicity. A total of 50 patients were enrolled between September 2013 and May 2019. Twelve patients received 5-fluorouracil, l-leucovorin and OX (FOLFOX) plus BV, 21 patients received capecitabine and OX plus BV, 10 patients received S-1 and OX plus BV and 7 patients received FOLFOX plus cetuximab or panitumumab. The median PFS was 11.5 months (95% confidence interval [CI] 8.3-16.0), the median OS was 45.4 months (95% CI 37.4-NA), and the RR was 56.0% (95% CI 42.3-68.8). Adverse events of grade ≥ 3 that occurred in ≥ 5% of cases were neutropenia in 6 patients (12%), peripheral sensory neuropathy in 5 patients (10%), diarrhea in 4 patients (8%), hypertension in 4 patients (8%), anorexia in 3 patients (6%) and allergic reactions in 3 patients (6%). First-line chemotherapy with re-introduction of OX more than 6 months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients.
Zenda S, Ota Y, Kiyota N, Okano S, Fujii M, et al.
Frontiers in oncology •
Induction chemotherapy (IC) is a treatment option for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). However, treatment with docetaxel, cisplatin, and 5-FU (TPF) followed by cisplatin and radiotherapy is controversial because of toxicity concerns. The aim of this phase II study was to assess the feasibility of docetaxel, cisplatin, and cetuximab (TPEx) followed by cetuximab and concurrent radiotherapy for LA SCCHN. We enrolled patients with histological evidence of squamous cell carcinoma of the oropharynx, hypopharynx, or larynx without distant metastases. IC comprised cisplatin (75 mg/m) and docetaxel (75 mg/m) on day 1, repeated every 3 weeks for up to three courses. Cetuximab was initiated at 400 mg/m, followed by 250 mg/m doses weekly until the end of radiotherapy. Radiotherapy (70 Gy/35 fr/7 w) was initiated after the last docetaxel administration. The primary endpoint was the rate of treatment completion. We enrolled 54 patients (median age, 58 years) between August 2013 and October 2015. Our patients were 49 males and 5 females with hypopharyngeal ( = 28), oropharyngeal ( = 19), or laryngeal ( = 7) cancers, and 48 of them had stage IV disease. The overall response rate was 72.2% with a median follow-up of 36.1 months and a 3-year overall survival of 90.7%. The treatment completion rate was 76%; 50 patients (93%) received ≥2 courses of IC, and 41 (76%) completed radiotherapy. The frequencies of grade ≥3 febrile neutropenia or allergy/infusion reactions were 39% and 11%, respectively. There was one treatment-related death. IC with TPEx followed by cetuximab with concurrent radiotherapy showed acceptable compliance for the treatment of LA SCCHN. However, high frequency of febrile neutropenia remains a challenge and further improvement in the management of TPEx is necessary. UMIN000009928.
