Successful switch to cisplatin-based chemotherapy in a patient with lung cancer who developed a carboplatin-induced hypersensitivity reaction.

INTRODUCTION: Platinum-based chemotherapy is the mainstay of first-line therapy for advanced-stage non-small cell lung cancer (NSCLC). Although carboplatin-induced hypersensitivity reactions (HSRs) commonly occur following multiple cycles of therapy, they are rarely observed during the first cycle of the treatment. CASE REPORT: Here, we report the case of a 70-year-old man with advanced-stage NSCLC who developed HSR possibly caused by carboplatin during the first cycle of induction with platinum-doublet chemotherapy plus pembrolizumab. The patient presented with bronchial obstruction due to a centrally located tumor. No driver mutations were detected, and the programmed death-ligand 1 expression ranged from 1% to 24%. Consequently, the patient was treated with pembrolizumab combined with carboplatin and paclitaxel. However, immediately after the start of carboplatin, the blood pressure and oxygen levels of the patient dropped and he began exhibiting an altered level of consciousness. These findings indicated carboplatin-induced anaphylaxis. Hypotension and oxygen desaturation improved following carboplatin discontinuation and normal saline administration. MANAGEMENT AND OUTCOME: The basophil activation test for both carboplatin and cisplatin was negative. Thus, the risk of anaphylaxis owing to both drugs was ruled out, and carboplatin was believed to have induced grade 3 HSR. Subsequently, carboplatin-based chemotherapy was switched to cisplatin-based chemotherapy. HSR was not observed during the four treatment cycles with pembrolizumab, cisplatin, and pemetrexed, and best response was partial response. DISCUSSION: Cisplatin-based chemotherapy could be used as an alternate treatment in patients with NSCLC who develop severe carboplatin-induced HSR.

TMEM207 hinders the tumour suppressor function of WWOX in oral squamous cell carcinoma.

The WW domain-containing oxidoreductase (WWOX) functions as a tumour suppressor in oral carcinogenesis. As aberrant TMEM207 expression may lead to tumour progression by hampering the tumour suppressor function of WWOX in various cancers, we explored the expression and pathobiological properties of TMEM207, focusing on the WWOX-mediated regulation of the HIF-1α pathway in oral squamous cell carcinoma (OSCC). TMEM207 immunoreactivity was detected in 40 of 90 OSCC samples but not in neighbouring non-tumorous epithelial tissues. Moreover, TMEM207 expression was significantly correlated with lymph node metastasis and poor prognosis. An in situ proximal ligation assay demonstrated the colocalization of TMEM207 and WWOX in invasive OSCC cells, especially glycogen-rich ones. Enforced expression of TMEM207 abrogated the binding of WWOX to HIF-1α, increased HIF-1α and GLUT-1 expression, even under normoxic conditions, and promoted tumour growth in a xenoplant assay using SAS tongue squamous cancer cells. In contrast, TMEM207 knockdown decreased GLUT-1 expression in two OSCC cell lines. As a whole, our findings indicate that the aberrant expression of TMEM207 contributes to tumour progression in OSCC, possibly via promoting aerobic glycolysis.

Pathobiological properties of the ubiquitin ligase Nedd4L in melanoma.

A recent global gene expression profiling study unexpectedly showed that activated oncogenic NRAS may recruit neural precursor cell expressed, developmentally downregulated 4L (Nedd4L; a human homologue of Nedd4-2) in cultured melanoma cells. However, whether Nedd4L was expressed in melanoma tissues or participated in melanoma carcinogenesis remains to be clarified. Here, we investigated the expression status of Nedd4L in human melanocytes, benign nevi and melanoma tissue specimens and subsequently attempted to determine the role of Nedd4L in melanoma cell growth. Immunohistochemical staining revealed that Nedd4L was not present in any non-tumorous melanocytes or in 18 benign nevi tissues, but it was detected in 34 of 79 cutaneous melanomas and 9 of 32 nodal metastatic melanomas. Downregulation of Nedd4L significantly reduced the growth of cultured G361 melanoma cells in vitro. Moreover, exogenous Nedd4L expression significantly promoted the growth of A2058 melanoma cells in vivo in a xenograft assay. The present findings indicate that Nedd4L expression may be increased to facilitate tumour growth in many melanomas.

Nuclear localization of LDL receptor-related protein 1B in mammary gland carcinogenesis.

LRP1B intracellular domain is released and transported to the nucleus; however, pathological consequences of this nuclear transport are largely unclear. We aimed to unravel the pathobiological significance of nuclear localization of LRP1B intracellular domain in mammary gland carcinogenesis. Immunohistochemical staining using antibodies for LRP1B intracellular domain was performed to determine LRP1B expression in 92 invasive ductal breast carcinomas. LRP1B immunoreactivity was detected in the surface membrane and cytoplasm of 60 of 92 invasive ductal carcinomas and in the nucleus of 15 of 92 carcinomas. Nuclear LRP1B was significantly associated with poor patient prognosis, particularly luminal A type breast cancer, where it was significantly related to nodal metastasis. Doxycycline-dependent nuclear expression of LRP1B intracellular domain was established in cultured breast cancer cells. Enforced nuclear expression significantly increased Matrigel invasion activity in MCF-7 and T47D luminal A breast cancer cells. Moreover, enforced nuclear expression of LRP1B intracellular domain facilitated MCF-7 cells growth in mammary fat pad of nude mice, which was supplemented with estrogen. Comprehensive microarray-based analysis demonstrated that nuclear expression of LRP1B intracellular domain significantly increased long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) expression, which facilitates breast cancer invasion with poor prognosis. Nuclear-localized LRP1B intracellular domain promoted breast cancer progression with poor prognosis, possibly through the NEAT1 pathway. Nuclear transport of LRP1B intracellular domain could be a therapeutic target for breast cancer patients. KEY MESSAGES: Nuclear LRP1B was significantly associated with poor patient prognosis. Nuclear LRP1B increased Matrigel invasion activity of breast cancer cells. Nuclear expression of LRP1B intracellular domain increased NEAT1 expression.

Major anthocyanins from purple asparagus (Asparagus officinalis).

Two major anthocyanins (A1 and A2) were isolated from peels of the spears of Asparagus officinalis cv. Purple Passion. They were purified by column, paper and high-performance liquid chromatographic separations, and their structures were elucidated by high-resolution Fourier transform ion cyclotron resonance mass spectrometry (HR-FT-ICR MS), 1H, 13C and two-dimensional NMR spectroscopic analyses and either acid or alkaline hydrolysis, respectively. A1 was identified as cyanidin 3-[3''-(O-beta-d-glucopyranosyl)-6''-(O-alpha-l-rhamnopyranosyl)-O-beta-d-glucopyranoside], whereas A2 was cyanidin 3-rutinoside, which is widely distributed in higher plants. Oxygen radical absorbance capacity (ORAC) assays proved their high antioxidant activities.

Expression of ZNF396 in basal cell carcinoma.

Zfp191 represses differentiation and keeps various cells in the stem/progenitor stage. Here, we report that a Zfp191 homolog protein, ZNF396, is expressed in basal cell carcinoma (BCC) and possibly represses the expression of a Notch system effector molecule, Hes1 (hairy and enhancer of split-1), and prevents BCC cells from undergoing Notch-mediated squamous cell differentiation. ZNF396 immunoreactivity was found in the nucleus of 35 of 38 cutaneous BCC and 4 of 74 squamous cell carcinoma tissue specimens. In non-tumorous epidermal tissues, ZNF396 immunoreactivity was restricted in basal cells. siRNA-mediated silencing of ZNF396 induced the expression of Notch2, Hes1, and involucrin in cultured BCC cells. Finally, we found that siRNA-mediated silencing of ZNF396 gene inhibited the proliferation of TE354.T basal cell carcinoma cells. ZNF396 might repress Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous differentiation in BCC.

Development and characterization of microsatellite markers for Lilium longiflorum (Liliaceae).

PREMISE OF THE STUDY: Ten microsatellite primers were developed to obtain information on genetic variation in Lilium longiflorum, a bulbous species showing high intraspecific genetic differentiation. • METHODS AND RESULTS: Of 61 microsatellite loci isolated using the dual suppression PCR technique, 10 loci were effective to characterize and estimate genetic variation in two populations of L. longiflorum. The number of alleles at each locus was different between the populations (averages = 3.2 and 10.3 alleles per locus), and the mean observed heterozygosity values were 0.245 and 0.732. • CONCLUSIONS: Our results demonstrate that there is significant genetic variation between the populations and that the microsatellite markers developed in this study will be useful tools for the investigation of the genetic structure and mating system of natural L. longiflorum populations.

Dietary kakrol (Momordica dioica Roxb.) flesh inhibits triacylglycerol absorption and lowers the risk for development of fatty liver in rats.

Kakrol (Momordica dioica Roxb.) is a cucurbitaceous vegetable native to India and Bangladesh. Bitter gourd (Momordica charantia Linn.), a species related to kakrol, has been shown to have pharmacological properties including antidiabetic and antisteatotic effects. In this study, we investigated the effect of dietary kakrol on lipid metabolism in rats. Sprague-Dawley rats were fed AIN-76 formula diets containing 3% freeze-dried powders of whole kakrol or bitter gourd for two weeks. Results showed significantly lowered liver cholesterol and triacylglycerol levels in rats fed on both diets. Fecal lipid excretion increased in rats fed the kakrol diet, and lymphatic transport of triacylglycerol and phospholipids decreased in rats fed the kakrol diet after permanent lymph cannulation. Furthermore, n-butanol extract from kakrol caused a significant concentration-dependent decrease in the pancreatic lipase activity in vitro. These results indicate that the mechanisms of action on lipid metabolism in kakrol and bitter gourd are different and that dietary kakrol reduces liver lipids by inhibiting lipid absorption.

Hybridization and asymmetric introgression between Rhododendron eriocarpum and R. indicum on Yakushima Island, southwest Japan.

We examined natural hybridization between two morphologically and ecologically divergent species on Yakushima Island-the light-purple flowered Rhododendron eriocarpum native to seaside habitats and the red flowered R. indicum native to riverside habitats. By investigation of morphological traits and amplified fragment length polymorphisms (AFLP) we found that hybrid individuals morphologically and genetically intermediate between the two species grow mainly in the seaside areas of the island. The degree of morphological and genetic variation was different among the seaside hybrid populations. Although most pollinator species were exclusive to one of the two flower color groups, the halictine bees of Lasioglossum were observed in both the color types. The crucial interspecific incompatibility after pollination has not been previously described. Geographic distance between the populations is likely to be an important primary factor in bringing about natural hybridization and determining the degree of introgression between R. eriocarpum and R. indicum. The fact that hybrids occur mostly in the seaside area on Yakushima Island indicates that asymmetrical introgression occurs from R. indicum to R. eriocarpum. Alternatively, strong habitat-mediated selection from recurrent floods may prevent the hybrids from colonizing riverside habitats.

Rhizome transition to storage organ is under phytochrome control in lotus (Nelumbo nucifera).

We examined photoperiodic response of lotus (Nelumbo nucifera) rhizome morphogenesis (its transition to a storage organ) by using seed-derived plants. Rhizome enlargement (increase in girth) was brought about under 8, 10 and 12 h photoperiods, whereas the rhizomes elongated under 13 and 14 h photoperiods. Rhizomes elongated under 14 h light regimes supplied as 8 h of natural light plus 6 h supplemental hours of white, yellow or red light, but similar treatments with supplemental blue, green or far red light, caused enlargement in girth of the rhizomes. A 2 h interruption of the night with white, yellow or red light, in plants entrained to 8 h photoperiod brought rhizome elongation, whereas 2 h-blue, green or far red light night breaks still resulted in rhizome increase in girth. The inhibitory effect of a red (R) light night break on rhizome increase in girth was reversed by a far-red (FR) light given immediately afterwards. Irradiation with R/FR/R inhibited the rhizome increase in girth. FR light irradiation following R/FR/R irradiation cancelled the effect of the last R light irradiation. It was demonstrated that the critical photoperiod for rhizome transition to storage organ is between 12 and 13 h photoperiod. It was also evident that the optimal light quality range for interruption of dark period (night break) is between yellow and red light and that a R/FR reversible reaction is observed. From these results, we propose that phytochrome plays an important role in photoperiodic response of rhizome increase in girth in lotus. This is the first report on phytochrome-dependent morphogenesis of storage organs in rhizomous plants.

Short photoperiod induces dormancy in Lotus (Nelumbo nucifera).

BACKGROUND AND AIMS: Lotus (Nelumbo nucifera) has been cultivated as an ornamental and food plant in Japan for more than 1000 years. As large areas are required for its cultivation (approximately 2 m2 per plant), physiological research, such as into the effect of environmental factors on dormancy, has not been well studied until recently. In this paper, seedlings were used to examine environmental factors affecting dormancy induction. METHODS: In a first experiment, seeds were sown from 6 April to 6 October at 2-month intervals, and cultivated for 2 months in an unheated greenhouse. In a second experiment, seeds were prepared for germination on 16 November and 16 May and the seedlings were grown at 25 or 30 degrees C under natural daylength in phytotron growth rooms. After 1 month, the seedlings were cultivated at 20, 25 or 30 degrees C for a further month. The number of leaves and rhizome branches on the main stem were counted, and growth of rhizomes on the main stem was calculated using a rhizome enlargement index (= maximum internode diameter/internode length) after 2 months of culture in both experiments. KEY RESULTS: Rhizomes elongated without enlargement when the seeds were sown in April and June. Sowing the seeds in August and October resulted in rhizome enlargement from the tenth and fifth internodes, respectively. Rhizomes enlarged in the November-sowing but elongated in the May-sowing irrespective of temperature treatments under natural daylength in the phytotron rooms. The seedlings cultivated from May at 25-30 degrees C for 2 months had more leaves, and more rhizome branches and nodes than those cultivated from November. CONCLUSIONS: Short days led to induced dormancy in lotus.