Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1, 2 and 4 in colorectal adenocarcinoma： Immunohistochemical analysis and correlation with clinicopathological factors

AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and Tie-2 receptors constitute a major class. Angiopoietin (Ang)-1 is known as a ligand of Tie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4 expression profile in human colorectal adenocarcinomas. METHODS: We examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and investigated the statistical correlation between the expressions of Ties and Angs and clinicopathological factors. RESULTS: Among the 96 cases of adenocarcinoma, 87 (90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76 cases (79.2%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2 and 4 proteins, respectively. Histologically, the expressions of Ties and Angs were variable. The expressions of Ties and Angs were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ties and Angs were highly expressed in human colorectal adenocarcinoma cells. CONCLUSION: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma.     

Endonasal flap suture-dacryocystorhinostomy (eFS-DCR): a new surgical technique for nasolacrimal duct obstruction (NLDO)

Conclusion: Endonasal flap suture-dacryocystorhinostomy (eFS- DCR) is a new and valuable technique for the treatment of nasolacrimal duct obstruction (NLDO). This technique could improve the success rate of endonasal DCR in comparison to external DCR. Objective: The standard procedure for NLDO is DCR. DCR can be performed via either an external or endonasal approach. External DCR is now regarded as the gold standard in the treatment of NLDO because of its higher success rate. However, we report a new endonasal surgical technique, eFS-DCR, and assess its efficacy by comparison with the standard endonasal DCR. Methods: We prospectively investigated a series of 62 consecutive patients with NLDO undergoing endonasal DCR. There were two surgical intervention groups: group 1 (24 patients, 28 sites) undergoing endonasal DCR without eFS; and group 2 (38 patients, 47 sites) undergoing eFS-DCR. Study end points were success rate, the ostium diameter (OD) of the lacrimal sac after DCR, and the duration of stent placement. We compared the two groups on these three points. Results: The success rate was 78.6% (22 of 28 sites) for group 1 (DCR without eFS) and 97.9% (46 of 47 sites) for group 2 (eFS-DCR). The ostium size in patients in group 2 was larger than that in group 1. The median time for the duration of stent placement was 42.5 days for group 1 and 31.5 days for group 2. There was a statistical difference (p < 0.01) in all these parameters between the two groups.     

Hormonal regulation of gonadotropin receptor mRNA in rat ovary during follicular growth and luteinization.

To investigate the regulation of the follicle-stimulating hormone (FSH) and luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor genes by gonadotropins, we examined the effect of pregnant mare's serum gonadotropin (PMSG) or PMSG-hCG on the expression of FSH and LH/hCG receptors in rat ovaries. After administration of PMSG, Northern blot analysis using the FSH receptor cDNA probe revealed that a major band of 2400 nucleotides was detected which reached the maximal level on day 3. On the other hand, the level of LH/hCG receptor mRNA, a major mRNA of 5400 nucleotides and minor species of 7500, 3600, 2300 and 1200 nucleotides, increased progressively during 4 days. Treatment with hCG resulted in a decrease of FSH and LH/hCG receptor mRNA levels, and the level of FSH receptor mRNA was completely suppressed. Although the level of LH/hCG receptor mRNA was also suppressed from 3 h to an almost undetectable level at 24 h after hCG injection, it recovered to the control level by 48 h and exceeded this level several fold by 72 h. The reappearance of LH/hCG receptors following desensitization was preceded by an increase in mRNA levels. These studies demonstrate that hormonal regulation of gonadotropin receptor mRNAs on rat ovary reflects the changes in gonadotropin receptor levels.     

Rectal Cancer With Disseminated Carcinomatosis of the Bone Marrow: Report of a Case

We report a rare case of disseminated carcinomatosis of the bone marrow from rectal cancer with disseminated intravascular coagulation (DIC). A 65-year-old man was admitted with melena and low back pain at rest. X-ray examination showed rectal cancer with multiple bone metastases. Laboratory examination showed severe anemia and DIC. Histologic examination showed disseminated carcinomatosis of the bone marrow. The DIC was considered to be caused by disseminated carcinomatosis of the bone marrow from rectal cancer, and we immediately started treatment with anti-DIC therapy and anticancer chemotherapy with the modified FOLFOX6 regimen (mFOLFOX6). After some response to therapy, the patient''s general condition deteriorated, and he died 128 days after admission. This is the first English report showing disseminated carcinomatosis of the bone marrow from colorectal cancer treated with mFOLFOX6.Key words: Bone marrow neoplasms, Rectal neoplasms, Disseminated intravascular coagulationBone metastases diffusely invading the bone marrow with disseminated intravascular coagulation (DIC) and microangiopathic hemolytic anemia (MHA) tend to accompany solid tumors; this condition is called disseminated carcinomatosis of the bone marrow,¹ and it is associated with an extremely poor prognosis. Among solid tumors, DIC is most commonly associated with breast cancer, prostate cancer, and lung cancer^2,3; carcinomatosis arising from colorectal cancer is rare.Herein we report on a patient with disseminated carcinomatosis of the bone marrow with rectal cancer who developed acute DIC and was treated with a modified FOLFOX6 regimen (mFOLFOX6). We also review 11 similar previously reported cases.^4–10     

Right bundle branch block without overt heart disease predicts higher risk of pacemaker implantation: The study of atomic-bomb survivors

Background

We investigated the clinical course of complete right bundle branch block (RBBB) or RBBB with axis deviation (AD) in terms of subsequent pacemaker implantation for high-degree atrioventricular (AV) block or sick sinus syndrome (SSS).

Methods and results

Among the 16,170 atomic-bomb survivors in our biennial health examination between July 1967 and December 2010, we detected 520 newly-acquired RBBB subjects with no organic heart disease, and selected 1038 age- (at RBBB diagnosis) and sex-matched subjects without RBBB to serve as comparison subjects. Multivariate Cox regression analysis was used to estimate the hazard ratios (HRs) for the risk of pacemaker implantation due to all causes, AV block or SSS between RBBB and comparison subjects and between RBBB subjects with and without AD. The risk of pacemaker implantation for RBBB was 4.79 (95% confidence interval [CI] 1.89–12.58; P = 0.001), 3.77 (95% CI, 1.09–13.07; P = 0.036), and 6.28 (95% CI, 1.24–31.73, P = 0.026) when implantation was for all causes, AV block and SSS, respectively. RBBB subjects with AD had a higher risk for all-cause pacemaker implantation than subjects without AD (HR, 3.03; 95% CI, 1.00–9.13, P = 0.049). RBBB subjects with AD were younger than subjects without AD at the time of RBBB diagnosis (59.4 ± 7.6 vs 74.4 ± 3.1 years old, P = 0.019), and their progression from diagnosis to pacemaker implantation took longer (15.1 ± 6.6 vs 6.4 ± 3.0 years, P = 0.032).

Conclusions

RBBB, especially with AD, progresses to AV block and SSS that requires pacemaker implantation; the mechanisms by which the conduction defect progresses differ among patients with and without AD.     

Tongue Pressure During Swallowing in Adults with Down Syndrome and Its Relationship with Palatal Morphology

In individuals with Down syndrome, hypotonicity of the tongue and an underdeveloped maxilla may lead to poor oral motor coordination, which adversely affects the oral phase of swallowing. This study aimed to evaluate the characteristics of pressure produced by the tongue against the hard palate during swallowing in individuals with Down syndrome. In addition, the relationship between tongue pressure and palatal morphology was examined. We studied nine adults with Down syndrome and ten healthy adults as controls. Tongue pressure while swallowing 5 mL water was recorded by a sensor sheet system with five measuring points attached to the hard palate. Palatal length, depth, width, curvature, and slope were measured by three-dimensional digital maxillary imaging. The order of onset of tongue pressure on the median line of the hard palate was the same in all participants, except for three with Down syndrome. The duration and maximal magnitude of tongue pressure on the median line in nine participants with Down syndrome were significantly shorter and lower than those of controls. In participants with Down syndrome, significant positive correlations were observed between the duration of tongue pressure at the mid-median part of the hard palate and palatal depth and width, and between the duration and maximal magnitude of tongue pressure at the posterior-median part and palatal length. These findings suggest that impaired tongue activity, poor tongue control, and constrained tongue motion due to a short and narrow palate contribute to swallowing difficulty in individuals with Down syndrome.     

Two new alkaloids from Crinum asiaticum var. japonicum

Journal of Natural Medicines - A new crinine-type alkaloid crijaponine A (1), a new galanthamine-type alkaloid crijaponine B (2), and 11 known alkaloids—ungeremine (3), lycorine (4),...     

Narrowband ultraviolet B phototherapy ameliorates acute graft-versus-host disease by a mechanism involving in vivo expansion of CD4+CD25+Foxp3+ regulatory T cells

Narrowband ultraviolet B phototherapy (NB-UVB) is a therapeutic alternative for haematopoietic stem cell transplantation-related skin graft-versus-host disease (GVHD). The beneficial effects of this intervention may be induced by direct irradiation of inflammatory cells in the skin; however, the putative involvement of indirect effects on systemic immunity has not been elucidated. To address this issue, 11 acute skin GVHD patients refractory to standard corticosteroid treatment and with no gut/liver involvement were treated with NB-UVB irradiation. The median number of treatments was 10 times, with a mean cumulative exposure of 6.36 J/cm². No other immunosuppressive therapy was initiated during irradiation. Eight patients achieved an objective complete response, two had a partial response, and one showed no change. None of the patients experienced progressive skin GVHD or newly diagnosed gut/liver GVHD. NB-UVB was well tolerated, with no patients discontinuing irradiation due to toxicity. We additionally demonstrated by flow cytometry that NB-UVB irradiation induces the increment of the proportion of regulatory T cell (Tregs) in patients’ peripheral blood. These results suggest that NB-UVB may exert beneficial effects on steroid-refractory skin GVHD through the expansion of Tregs.     

Imaging and histopathological evaluation of a cystlike formation in subchondral insufficiency fracture of the femoral head: A case report and literature review

INTRODUCTION

In the majority of subchondral insufficiency fractures (SIFs) of the femoral head, T₁-weighted magnetic resonance imaging shows an irregular, serpiginous, low-intensity band that is convex to the articular surface. We report a case of a cystlike formation in SIF of the femoral head in an elderly woman.

PRESENTATION OF CASE

A 71-year-old woman reported right hip pain without any history of antecedent trauma. The initial radiograph showed a slight narrowing of the joint space in the right hip. The patient was treated with conservative therapy for 2 months. Radiographs obtained 3 months after the onset of pain showed non-progressive joint-space narrowing. T₁-weighted magnetic resonance images obtained 2 months after pain onset revealed a round, cystlike, low-intensity area just beneath the articular cartilage. The patient underwent total hip arthroplasty. Histopathological examination showed fracture callus and granulation tissue in the subchondral area, surrounded by vascular-rich granulation tissue and fibrous tissue, which corresponded to the round, low-intensity band observed on the T₁-weighted image.

DISCUSSION

This case was a rare SIF of the femoral head which had a cystlike formation with a low signal intensity on T₁-weighted images and a very high signal intensity on STIR sequences in the superolateral portion of the femoral head, surrounded by a pattern of edema in the bone marrow. To our knowledge, no similar cases were cited in the literature.

CONCLUSION

It is important for surgeons to keep in mind that sometimes SIFs of the femoral head can appear as a round cystlike formation.     

Oral vaccination against HPV E7 for treatment of cervical intraepithelial neoplasia grade 3 (CIN3) elicits E7-specific mucosal immunity in the cervix of CIN3 patients

Background

Cervical intraepithelial neoplasia grade 3 (CIN3) is a mucosal precancerous lesion caused by high-risk human papillomavirus (HPV). Induction of immunological clearance of CIN3 by targeting HPV antigens is a promising strategy for CIN3 therapy. No successful HPV therapeutic vaccine has been developed.

Methods

We evaluated the safety and clinical efficacy of an attenuated Lactobacillus casei expressing modified full-length HPV16 E7 protein in patients with HPV16-associated CIN3. Ten patients were vaccinated orally during dose optimization studies (1, 2, 4, or 6 capsules/day) at weeks 1, 2, 4, and 8 (Step 1). Seven additional participants were only tested using the optimized vaccine formulation (Step 2), giving a total of 10 patients who received optimized vaccination. Cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were collected and E7 specific interferon-γ-producing cells were counted (E7 cell-mediated immune responses: E7-CMI) by ELISPOT assay. All patients were re-evaluated 9 weeks after initial vaccine exposure using cytology and biopsy to assess pathological efficacy.

Results

No patient experienced an adverse event. E7-CMI in both CxLs and PBMCs was negligible at baseline. All patients using 4–6 capsules/day showed increased E7-CMI in CxLs, whereas patients using 1–2 capsules/day did not. No patient demonstrated an increase in E7-CMI in their PBMCs. In comparison between patients of cohorts, E7-CMI at week 9 (9 wk) in patients on 4 capsules/day was significantly higher than those in patients on 1, 2, or 6 capsules/day. Most patients (70%) taking the optimized dose experienced a pathological down-grade to CIN2 at week 9 of treatment. E7-CMI in CxLs correlated directly with the pathological down-grade.

Conclusions

Oral administration of an E7-expressing Lactobacillus-based vaccine can elicit E7-specific mucosal immunity in the uterine cervical lesions. We are the first to report a correlation between mucosal E7-CMI in the cervix and clinical response after immunotherapy in human mucosal neoplasia.