Cell surface tetraspanin CD9 mediates chemoresistance in small cell lung cancer

Small cell lung cancer (SCLC) is an aggressive malignancy with extremely high mortality due to the appearance of widespread metastases early in its clinical course and rapid acquisition of chemoresistance after initial therapy. A theory of cell adhesion-mediated drug resistance is thought to be a principal mechanism in which extracellular matrix proteins provide a survival advantage against cytotoxic drug-induced apoptosis. We found that the tetraspanin family member CD9 was expressed preferentially in SCLC tumors and metastases from three of seven relapsed patients, whereas chemona?ve primary tumors from 16 patients were CD9 negative with only one exception. Additionally, CD9 was highly expressed on SCLC cell lines rendered resistant to cisplatin or etoposide, and was upregulated in parental chemosensitive cells within 48 hours after exposure to either of these compounds. CD9-expressing chemoresistant SCLC cells adhered more tightly to fibronectin via β1 integrin, but they were less motile than the respective chemosensitive parental lines. Notably, treatment of the chemoresistant cells with chemokine CXCL12 downregulated CD9 and transiently restored motility. Moreover, selective targeting of CD9 by treatment with specific monoclonal antibody ALB6 or a small interfering RNA triggered apoptosis in the chemoresistant cells. Taken together, our findings implicate CD9 in the cell adhesion-mediated drug resistance mechanism, highlighting CD9 as an attractive therapeutic target to improve therapeutic outcomes in SCLC.     

Value of religious care for relief of psycho‐existential suffering in Japanese terminally ill cancer patients: the perspective of bereaved family members

Objective: This study aimed to clarify the experience of bereaved family members of cancer patients regarding the usefulness of religious care (perceived usefulness). The value of this care to palliate psycho‐existential suffering in future patients was also examined (predicted usefulness). Methods: A questionnaire was sent to 592 bereaved family members of cancer patients who were admitted to certified palliative care units in Japan. Responses were obtained from 378 families, indicating whether the patient received religious care, the perceived usefulness of the care, and its predicted usefulness for palliation of psycho‐existential suffering. Results: About 25% (N=83) indicated that the patient had received religious care, whereas 75% (N=255) had not received it. Families of patients who had received religious care evaluated pastoral care workers (86%), religious services (82%), and religious music (80%) as ‘very useful’ or ‘useful’. Families predicted usefulness of religious care for future patients: attending a religious service (very useful or useful, 56%; not useful or harmful, 44%), a religious atmosphere (48%, 52%), meeting with a pastoral care worker (50%, 50%), and religious care by physicians (26%, 74%), and nurses (27%, 73%). Families with a religion were significantly more likely to rate religious care as useful for future patients. Conclusions: Families of patients who received religious care generally evaluated this care to be very useful or useful. For future patients, some families felt that religious care would be useful, but some did not. In Japan, religious care is more likely to provide benefits to patients who have a religion. Copyright © 2009 John Wiley & Sons, Ltd.     

Assessment of the relationship between stenosis severity and distribution of coronary artery stenoses on multislice computed tomographic angiography and myocardial ischemia detected by single photon emission computed tomography

Background

The relationship between luminal stenosis measured by coronary CT angiography (CCTA) and severity of stress-induced ischemia seen on single photon emission computed tomographic myocardial perfusion imaging (SPECT-MPI) is not clearly defined. We sought to evaluate the relationship between stenosis severity assessed by CCTA and ischemia on SPECT-MPI.

Methods and Results

ECG-gated CCTA (64 slice dual source CT) and SPECT-MPI were performed within 6 months in 292 patients (ages 26-91, 73% male) with no prior history of coronary artery disease. Maximal coronary luminal narrowing, graded as 0, ≥25%, 50%, 70%, or 90% visual diameter reduction, was consensually assessed by two expert readers. Perfusion defect on SPECT-MPI was assessed by computer-assisted visual interpretation by an expert reader using the standard 17 segment, 5 point-scoring model (stress perfusion defect of ≥5% = abnormal). By SPECT-MPI, abnormal perfusion was seen in 46/292 patients. With increasing stenosis severity, positive predictive value (PPV) increased (42%, 51%, and 74%, P = .01) and negative predictive value was relatively unchanged (97%, 95%, and 91%) in detecting perfusion abnormalities on SPECT-MPI. In a receiver operator curve analysis, stenosis of 50% and 70% were equally effective in differentiating between the presence and absence of ischemia. In a multivariate analysis that included stenosis severity, multivessel disease, plaque composition, and presence of serial stenoses in a coronary artery, the strongest predictors of ischemia were stenosis of 50-89%, odds ratio (OR) 7.31, P = .001, stenosis ≥90%, OR 34.05, P = .0001, and serial stenosis ≥50% OR of 3.55, P = .006.

Conclusions

The PPV of CCTA for ischemia by SPECT-MPI rises as stenosis severity increases. Luminal stenosis ≥90% on CCTA strongly predicts ischemia, while <50% stenosis strongly predicts the absence of ischemia. Serial stenosis of ≥50% in a vessel may offer incremental value in addition to stenosis severity in predicting ischemia.     

DNA vaccine expressing HIV-1 gp120/immunoglobulin fusion protein enhances cellular immunity

In this study, we explored the possibility of augmenting human immunodeficiency virus (HIV) gp120-specific cell-mediated immune responses in mice by means of a DNA vaccine encoding a mouse Ig Fcγ2a fragment fused with gp120 (gp120-Ig, Ig-gp120). Western blotting analysis revealed that the HIV gp120 protein expression efficiency was higher in cells transfected with the gp120-Ig-coding plasmid (pGp120Ig) than in those transfected with the gp120 and Ig-gp120 expression plasmids (pGp120 and pIgGp120, respectively). pGp120Ig elicited more HIV-specific CD8 T cells and effector memory CD8 T cells than pGp120 in immunized mice. Furthermore, pGp120Ig significantly reduced the viral load after challenge with an HIV Env gp160-expressing vaccinia virus. These results demonstrate that covalent antigen modification with an Ig sequence can modulate antigen-specific cellular immune responses. The approach may be useful for vaccine development.     

Influenza A (H5N1) Viruses from Pigs, Indonesia

Pigs have long been considered potential intermediate hosts in which avian influenza viruses can adapt to humans. To determine whether this potential exists for pigs in Indonesia, we conducted surveillance during 2005–2009. We found that 52 pigs in 4 provinces were infected during 2005–2007 but not 2008–2009. Phylogenetic analysis showed that the viruses had been introduced into the pig population in Indonesia on at least 3 occasions. One isolate had acquired the ability to recognize a human-type receptor. No infected pig had influenza-like symptoms, indicating that influenza A (H5N1) viruses can replicate undetected for prolonged periods, facilitating avian virus adaptation to mammalian hosts. Our data suggest that pigs are at risk for infection during outbreaks of influenza virus A (H5N1) and can serve as intermediate hosts in which this avian virus can adapt to mammals.     

Intussusception due to rectal adenocarcinoma in a young adult: A case report

An intussusception due to colonic adenocarcinoma has sometimes been reported. However, to the best of our knowledge, reports of intussusception due to rectal adenocarcinoma are extremely rare. In this report, the case of a young man with rectal adenocarcinoma causing intussusception is described. A 24-year-old man visited a hospital complaining of abdominal pain, and an upper rectal cancer was diagnosed by colonoscopy. Computed tomography showed intussusception caused by a large tumor in the pelvis and absence of distant metastases. Locally advanced rectal cancer causing intussusception was diagnosed, and a low anterior resection was performed. Intraoperatively, repair of the invagination could not be accomplished easily; therefore, the repair was abandoned. Instead, the tumor was removed en bloc to avoid dissemination of the cancer. Histopathologically, the tumor was diagnosed as a poorly differentiated adenocarcinoma, pStage IIA. The patient has no evidence of recurrence at 10 mo after the operation.     

Prevention of esophageal strictures after endoscopic submucosal dissection

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have recently been accepted as less invasive methods for treating patients with early esophageal cancers such as squamous cell carcinoma and dysplasia of Barrett’s esophagus. However, the large defects in the esophageal mucosa often cause severe esophageal strictures, which dramatically reduce the patient’s quality of life. Although preventive endoscopic balloon dilatation can reduce dysphagia and the frequency of dilatation, other approaches are necessary to prevent esophageal strictures after ESD. This review describes several strategies for preventing esophageal strictures after ESD, with a particular focus on anti-inflammatory and tissue engineering approaches. The local injection of triamcinolone acetonide and other systemic steroid therapies are frequently used to prevent esophageal strictures after ESD. Tissue engineering approaches for preventing esophageal strictures have recently been applied in basic research studies. Scaffolds with temporary stents have been applied in five cases, and this technique has been shown to be safe and is anticipated to prevent esophageal strictures. Fabricated autologous oral mucosal epithelial cell sheets to cover the defective mucosa similarly to how commercially available skin products fabricated from epidermal cells are used for skin defects or in cases of intractable ulcers. Fabricated autologous oral-mucosal-epithelial cell sheets have already been shown to be safe.     

Pancreaticoduodenectomy following total gastrectomy:A case report and literature review

We present a case of afferent loop syndrome(ALS)occurring after pancreaticoduodenectomy(PD)in a patient who had previously undergone total gastrectomy(TG),and review the English-language literature concerning reconstruction procedures following PD in patients who had undergone TG.The patient was a69-year-old man who had undergone TG reconstruction by a Roux-en-Y method at age 58 years.The patient underwent PD for pancreas head adenocarcinoma.A jejunal limb previously made at the prior TG was used for pancreaticojejunostomy and hepaticojejunostomy.Despite normal patency of the hepaticojejunostomy,he suffered from repeated postoperative cholangitis which was brought on by ALS due to shortness of the jejunal limb(15 cm in length).We therefore performed receliotomy in which the hepaticojejunostomy was disconnected and reconstructed using a new Y limb 40-cm in length constructed in a double Roux-en-Y fashion.The refractory cholangitis resolved immediately after the receliotomy and did not recur.Review of the literature revealed the lack of any current consensus for a standard procedure for reconstruction following PD in patients who had previously undergone TG.This issue warrants further attention,particularly given the expected future increase in the number of PDs in patients with a history of gastric cancer.