Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers

BACKGROUND: Nectin-2 is a Ca(2+)-independent cell-cell adhesion molecule that is one of the plasma membrane components of adherens junctions. However, little has been reported about the involvement of Nectin-2 in cancer. METHODS: To determine the expression of Nectin-2 in cancer tissues and cancer cell lines, we performed gene expression profile analysis, immunohistochemistry studies, and flow cytometry analysis. We also investigated the potential of this molecule as a target for antibody therapeutics to treat cancers by generating and characterizing an anti-Nectin-2 rabbit polyclonal antibody (poAb) and 256 fully human anti-Nectin-2 monoclonal antibodies (mAbs). In addition, we tested anti-Nectin-2 mAbs in several in vivo tumor growth inhibition models to investigate the primary mechanisms of action of the mAbs. RESULTS: In the present study, we found that Nectin-2 was over-expressed in clinical breast and ovarian cancer tissues by using gene expression profile analysis and immunohistochemistry studies. Nectin-2 was over-expressed in various cancer cell lines as well. Furthermore, the polyclonal antibody specific to Nectin-2 suppressed the in vitro proliferation of OV-90 ovarian cancer cells, which express endogenous Nectin-2 on the cell surface. The anti-Nectin-2 mAbs we generated were classified into 7 epitope bins. The anti-Nectin-2 mAbs demonstrated antibody-dependent cellular cytotoxicity (ADCC) and epitope bin-dependent features such as the inhibition of Nectin-2-Nectin-2 interaction, Nectin-2-Nectin-3 interaction, and in vitro cancer cell proliferation. A representative anti-Nectin-2 mAb in epitope bin VII, Y-443, showed anti-tumor effects against OV-90 cells and MDA-MB-231 breast cancer cells in mouse therapeutic models, and its main mechanism of action appeared to be ADCC. CONCLUSIONS: We observed the over-expression of Nectin-2 in breast and ovarian cancers and anti-tumor activity of anti-Nectin-2 mAbs via strong ADCC. These findings suggest that Nectin-2 is a potential target for antibody therapy against breast and ovarian cancers

Using NU-KNIT® for hemostasis around recurrent laryngeal nerve during transthoracic esophagectomy with lymphadenectomy for esophageal cancer

BACKGROUND: We thought that using electrocautery for hemostasis caused recurrent laryngeal nerve palsy. We reflected the prolonged use of electrocautery and employed NU-KNIT® to achieve hemostasis nearby the recurrent laryngeal nerve. We assessed that using NU-KNIT® hemostasis prevented or not postoperative recurrent laryngeal nerve palsy, retrospectively. The present study was evaluated to compare using electrocautery hemostasis with using NU-KNIT® hemostasis during lymphadenectomy along recurrent laryngeal nerve. The variables compared were morbidity rate of recurrent laryngeal nerve palsy, operation time, and blood loss. RESULTS: We use NU-KNIT® to achieve hemostasis without strong compression. This group is named group N. On the other hand, we use electrocautery to achieve hemostasis. This group is named group E. Complication rate of recurrent laryngeal nerve palsy was higher in group E (55.6%) than group N (5.3%) (p = 0.007). CONCLUSIONS: Even hemostasis using NU-KNIT® was slightly more time-consuming than using electrocautery, we concluded that it would be useful to prevent recurrent laryngeal nerve palsy

Primary placement technique of jejunostomy using the entristar™ skin-level gastrostomy tube in patients with esophageal cancer

<p>Abstract</p> <p>Background</p> <p>We developed a skin-level jejunostomy tube (SLJT) procedure for patients undergoing esophagectomy using a skin-level gastrostomy tube (G-tube) (Entristar™; Tyco Healthcare, Mansfield, Mass), in order to improve their nutrition status and quality of life (QOL). We describe the procedure and the adverse effects of SLJT in patients with esophageal cancer (EC).</p> <p>Methods</p> <p>Over a 24-month period (March 2008 to March 2010), there were 16 patients (mean age: 61.8 years; age range: 49-75 years; 15 men, 1 woman) who had Stage II or III EC. Primary jejunostomy was performed under general anesthesia during esophagectomy. The technical success and the immediate and delayed complications of the procedure were recorded.</p> <p>Jejunostomy techniques</p> <p>SLJT placement using the G-tube (20Fr) was performed 20 cm from the Treitz ligament on the side opposing the jejunal mesenterium. The internal retention bolster was exteriorized through an incision in the abdominal wall. A single purse string suture using a 4-0 absorbable suture was performed. The internal retention bolster was then inserted into the jejunal lumen via the small incision. The intestine adjacent to the tube was anchored to the peritoneum using a single stitch.</p> <p>Results</p> <p>The SLJT was successfully inserted in all 16 patients. No early complications were documented. Follow-up for a median of 107 days (range, 26-320 days) revealed leakage to the skin in four patients, including superficial wound infections in two patients. There were no cases of obstruction of the tube or procedure-related death.</p> <p>Conclusions</p> <p>This SLJT placement technique using the G-tube is a safe procedure in patients with EC and allows the creation of a long-term feeding jejunostomy.</p

Disease-specific autoantibody production in the lungs and salivary glands of anti-synthetase syndrome

Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody–positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases

Evaluation of the Total Design Method in a survey of Japanese dentists

BACKGROUND: This study assessed the application of the Total Design Method (TDM) in a mail survey of Japanese dentists. The TDM was chosen because survey response rates in Japan are unacceptably low and the TDM had previously been used in a general population survey. METHODS: Four hundred and seventy eight dentist members of the Okayama Medical and Dental Practitioner's Association were surveyed. The nine-page, 27-item questionnaire covered dentist job satisfaction, physical practice, and dentist and patient characteristics. Respondents to the first mailing or the one-week follow-up postcard were defined as early responders; others who responded were late responders. Responder bias was assessed by examining age, gender and training. RESULTS: The overall response rate was 46.7% (223/478). The response rates by follow-up mailing were, 18% after the first mailing, 35.4% after the follow-up postcard, 42.3% after the second mailing, and 46.7% after the third mailing. Respondents did not differ from non-respondents in age or gender, nor were there differences between early and late responders. CONCLUSION: The application of TDM in this survey of Japanese dentists produced lower rates of response than expected from previous Japanese and US studies

Upper abdominal body shape is the risk factor for postoperative pancreatic fistula after splenectomy for advanced gastric cancer: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Postoperative pancreas fistula (POPF) is a major complication after total gastrectomy with splenectomy. We retrospectively studied the effects of upper abdominal shape on the development of POPF after gastrectomy.</p> <p>Methods</p> <p>Fifty patients who underwent total gastrectomy with splenectomy were studied. The maximum vertical distance measured by computed tomography (CT) between the anterior abdominal skin and the back skin (U-APD) and the maximum horizontal distance of a plane at a right angle to U-APD (U-TD) were measured at the umbilicus. The distance between the anterior abdominal skin and the root of the celiac artery (CAD) and the distance of a horizontal plane at a right angle to CAD (CATD) were measured at the root of the celiac artery. The CA depth ratio (CAD/CATD) was calculated.</p> <p>Results</p> <p>POPF occurred in 7 patients (14.0%) and was associated with a higher BMI, longer CAD, and higher CA depth ratio. However, CATD, U-APD, and U-TD did not differ significantly between patients with and those without POPF. Logistic-regression analysis revealed that a high BMI (≥25) and a high CA depth ratio (≥0.370) independently predicted the occurrence of POPF (odds ratio = 19.007, p = 0.002; odds ratio = 13.656, p = 0.038, respectively).</p> <p>Conclusion</p> <p>Surgical procedures such as total gastrectomy with splenectomy should be very carefully executed in obese patients or patients with a deep abdominal cavity to decrease the risk of postoperative pancreatic fistula. BMI and body shape can predict the risk of POPF simply by CT.</p