Automated prediction of dosimetric eligibility of patients with prostate cancer undergoing intensity-modulated radiation therapy using a convolutional neural network

The quality of radiotherapy has greatly improved due to the high precision achieved by intensity-modulated radiation therapy (IMRT). Studies have been conducted to increase the quality of planning and reduce the costs associated with planning through automated planning method; however, few studies have used the deep learning method for optimization of planning. The purpose of this study was to propose an automated method based on a convolutional neural network (CNN) for predicting the dosimetric eligibility of patients with prostate cancer undergoing IMRT. Sixty patients with prostate cancer who underwent IMRT were included in the study. Treatment strategy involved division of the patients into two groups, namely, meeting all dose constraints and not meeting all dose constraints, by experienced medical physicists. We used AlexNet (i.e., one of common CNN architectures) for CNN-based methods to predict the two groups. An AlexNet CNN pre-trained on ImageNet was fine-tuned. Two dataset formats were used as input data: planning computed tomography (CT) images and structure labels. Five-fold cross-validation was used, and performance metrics included sensitivity, specificity, and prediction accuracy. Class activation mapping was used to visualize the internal representation learned by the CNN. Prediction accuracies of the model with the planning CT image dataset and that with the structure label dataset were 56.7?±?9.7% and 70.0?±?11.3%, respectively. Moreover, the model with structure labels focused on areas associated with dose constraints. These results revealed the potential applicability of deep learning to the treatment planning of patients with prostate cancer undergoing IMRT.     

A 13-week subchronic oral toxicity study of chlorophyll in F344 rats

A 13-week subchronic toxicity study of chlorophyll (containing 40% oil) was performed in both sexes of F344 rats by feeding of CRF-1 powder diet containing 0, 0.18%, 0.55%, 1.66% and 5%, and vehicle (oil) alone. No animals died during the administration period and no changes in body weights and food intakes were found in any dosed groups. Some hematological, serum biochemical and histopathological changes were observed for the 5%-treated group, but these did not suggest obvious toxicity. These findings indicate that the treatment with 1.66% chlorophyll in diet for 13 weeks does not cause any changes in rats and the 5% feeding is not obviously toxic.     

Overexpression of MDM2 in a sclerosing epithelioid fibrosarcoma: genetic, immunohistochemical and ultrastructural study of a case

Sclerosing epithelioid fibrosarcoma (SEF) is an extremely rare soft-tissue neoplasm. Here, we describe the molecular genetic alterations and histological, immunohistochemical and ultrastructural features of a primary SEF arising in the retroperitoneum. The tumor consisted of uniform small round to ovoid epithelioid cells, arranged in nests and cords and surrounded by a prominent hyalinized collagenous matrix. The tumor cells expressed only vimentin. Ultrastructurally, the tumor cells showed features of fibroblasts, with an abundant rough endoplasmic reticulum in the cytoplasm. Neither p53 gene mutations nor p53 protein overexpression were detected, but more than 70% of all tumor cells showed strong immunoreactivity with murine double minute 2 (MDM2). Our results suggest that MDM2 overexpression is likely to play a role in tumorigenesis in this lesion in p53-dependent or p53-independent pathways. To our knowledge, the present study is the first molecular genetic study of this rare lesion. Further studies will be necessary to clarify the molecular basis of tumorigenesis of this rare lesion.     

Genome-wide analyses on loss of heterozygosity in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor survival rate. Identifying the tumor suppressor gene (TSG) loci by genomic studies is an important step to uncover the molecular mechanisms involved in HNSCC pathogenesis. We therefore performed comprehensive analyses on loss of heterozygosity (LOH) using a genome-wide panel of 191 microsatellite markers in 22 HNSCC samples. We found 53 markers with significantly high LOH (>30%) on 21 chromosomal arms; the highest values of those were observed on 3p, 9p, 13q, 15q, and 17p, corresponding to D3S2432 (67%), D9S921-D9S925 (67%) and GATA62F03 (86%), D13S1493 (60%), D15S211 (62%), and D17S1353 (88%), respectively. Fifteen hot spots of LOH were defined in 13 chromosomal arms: 2q22-23, 4p15.2, 4q24-25, 5q31, 8p23, 9p23-24, 9q31.3, 9q34.2, 10q21, 11q21-22.3, 14q11-13, 14q22.3, 17p13, 18q11, and 19q12 as loci reported previously in HNSCCs. Furthermore, we identified five novel hot spots of LOH on three chromosomal arms in HNSCC at 2q33 (D2S1384), 2q37 (D2S125), 8q12-13 (D8S1136), 8q24 (D8S1128), and 15q21 (D15S211). In conclusion, our comprehensive allelotype analyses have unveiled and confirmed a total of 20 possible TSG loci that could be involved in the development of HNSCC. These results provide useful clues for identification of putative TSGs involved in HNSCC by fine mapping of the suspected regions and subsequent analysis for functional genes.     

Suppressive effect of acupuncture on delayed type hypersensitivity to trinitrochlorobenzene and involvement of opiate receptors.

We reported previously that electroacupuncture (Acu) at an acu-point equivalent to GV-4 in mice either enhanced or suppressed the delayed type hypersensitivity (DTH) to 2,4,6-trinitrochlorobenzene (TNCB, picryl chloride) depending on the time of treatment. We report here the suppression of the efferent phase of DTH to TNCB by Acu in mice. In 7- to 9-week-old male BALB/c, C57BL/6 and ddY mice, significant suppression of the DTH was observed when Acu had been applied once per day for three consecutive days before TNCB challenge. When Acu had been applied a single, significant suppression also occurred. Application to another point (at a middle area of the femoral muscle) failed to suppress the DTH to TNCB. This Acu-evoked DTH suppression was blocked dose-relatedly by pretreatment of systemic naloxone hydrochloride, indicating that opioid receptor-mediated mechanisms are involved in this immune response.     

Localized lymphoid hyperplasia of the rectum resembling polypoid mucosa-associated lymphoid tissue lymphoma: a report of three cases

Histologically, benign lymphoid hyperplasia of the rectum is usually characterized by large lymphoid follicles with active germinal centers and by a narrow surrounding mantle zone and marginal zone (MZ). We report here three cases of benign lymphoid hyperplasia of the rectum associated with prominent marginal zone hyperplasia, which caused serious difficulty in the differential diagnosis from the polypoid type of mucosa-associated lymphoid tissue (MALT) lymphoma. Colonoscopy demonstrated small sessile polyps in all three cases. Histologically, the lesions were characterized by a hyperplastic germinal center and expanded MZs. The expanded MZs contained numerous monocytoid B-cells (MBC) and scattered large transformed B-cells. Initially, combined colonoscopic and histological findings strongly supported a diagnosis of polypoid MALT-type lymphoma of the rectum. However, there were neither colonized lymphoid follicles nor lymphoepithelial lesions in any of the three lesions. MBCs and large transformed B-lymphocytes were CD43- and bcl-2-. Moreover, immunohistochemical and genotypic studies proved the polytypic nature of the B-lymphocytes in all three lesions. The present cases indicated that benign lymphoid hyperplasia of the rectum should be included in the differential diagnosis for polypoid MALT-type lymphoma of the rectum.     

Bikunin Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Induction in Macrophages

Bikunin, a Kunitz-type protease inhibitor, exhibits anti-inflammatory activity in protection against cancer and inflammation. To investigate the molecular mechanism of this inhibition, we analyzed the effect of bikunin on tumor necrosis factor alpha (TNF-α) production in human peripheral mononuclear cells stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Here, we show the following results. (i) LPS induced TNF-α expression in time- and dose-dependent manners through phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase pathways. (ii) Bikunin inhibits LPS-induced up-regulation of TNF-α protein expression in a dose-dependent manner, reaching 60% inhibition at the highest doses of bikunin tested (5.0 μM). (iii) Inhibition by bikunin of TNF-α induction correlates with the suppressive capacity of ERK1/2, JNK, and p38 signaling pathways, implicating repressions of at least three different signals in the inhibition. (iv) Bikunin blocks the induction of TNF-α target molecules interleukin-1β (IL-1β) and IL-6 proteins. (v) Bikunin is functional in vivo, and this glycoprotein blocks systemic TNF-α release in mice challenged with LPS. (vi) Finally, bikunin can prevent LPS-induced lethality. In conclusion, bikunin significantly inhibits LPS-induced TNF-α production, suggesting a mechanism of anti-inflammation by bikunin through control of cytokine induction during inflammation. Bikunin might be a candidate for the treatment of inflammation, including septic shock.