To determine the possible functional significance of CD40 expression on human non-small cell lung carcinomas and to assess the potential of CD40 as a therapeutic target, 18 lung tumor cell lines were established from biopsy tissues and were monitored for phenotypic changes on the cell surface and alterations in tumor cell proliferation after the ligation of CD40 with a trimeric fusion protein complex of CD40 ligand (CD40Lt). CD40 cross-linking resulted in up to a 6-fold increase in the surface expression of major histocompatibility complex (MHC) class I, Fas and intracellular adhesion molecule (ICAM)-1 in a subset of tumors expressing the highest levels of CD40. Suppression of tumor proliferation was seen after the ligation of CD40 on CD40Lt-responsive cell lines. The suppression was dose dependent, reversible and resulted from a delay of the tumor cells entering S-phase. No change in the cell phenotype or in proliferation were observed in CD40-negative tumors or in tumors expressing moderateto-low levels of CD40 after incubation with CD40Lt. CD40-negative tumors transfected with the CD40 gene expressed high levels of CD40 on their surface, but were also unresponsive to CD40Lt cross-linking of CD40. Our data establish that CD40 is required (but not sufficient) for transducing a signal that results in phenotypic changes in human lung tumors and suppression in their proliferation. We conclude that CD40 on non-small cell lung tumors may represent a potential therapeutic target, but only on a subset of the CD40؉ tumors. CD40, a molecule that has been recognized on B cells, dendritic cells and monocytes, is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily of molecules that include Fas and CD30. 1-4 CD40 is known to play a critical role in normal B-cell and dendritic cell development and function and in the survival, activation, differentiation and apoptosis of cells. 2,5 The ligand for CD40 (CD154) is transiently expressed on activated T cells. 2,5 The CD40 molecule is also expressed on other normal cells including fibroblasts and basal cells of the skin and on human neoplastic cells, that is, carcinomas of the colon, bladder, prostate, breast ovary and melanomas. 6 -11 Although the consequences and functional significance of CD40 ligation on B cells have been extensively studied, comparatively little is known about the effects of CD40 cross-linking on other cell types. CD40 engagement has been shown to inhibit the growth of primary epithelial cells in vitro and to induce differentiation, 12-14 and the ligation of CD40 on normal keratinocytes results in phenotypic changes such as enhanced secretion of interleukin-6 (IL-6) and TNF-␣ and up-regulation of intracellular adhesion molecule (ICAM)-1. 14 -16 Very little is known about the function of CD40 on neoplastic cells, and the effects of CD40 ligation on tumors has not been studied extensively.Because CD40 appears to play a significant role in the activation, proliferation and differentiation of normal cells, we have investi...

We report herein the case of a 77-year-old woman found to have mixed medullary-papillary carcinoma in the right thyroid with lymph node metastases 30 years after a left thyroidectomy. The preoperative values of serum calcitonin and carcinoembryonic antigen (CEA) were high, and fine-needle aspiration biopsy revealed class V, which led us to suspect papillary carcinoma. A right thyroidectomy with dissection of the right neck lymph nodes was performed. Histopathological examination of the tumor specimens revealed gradual borders between medullary carcinoma and papillary carcinoma with positive immunohistochemical staining to calcitonin, chromogranin A, CEA, and thyroglobulin. The serum levels of calcitonin and CEA decreased to normal after the operation. The point mutation of the RET proto-oncogene was found to be negative by a DNA analysis of the peripheral leukocytes. This cancer seemed not to be associated with multiple endocrine neoplasia type 2 syndrome. The presence of both medullary and papillary components in the thyroid with lymph node metastases is rare and may suggest that the tumor had arisen from a common stem cell.

BackgroundRecently, the use of taxane-based regimens before anthracycline-based regimens has been shown to achieve high pathological complete response (pCR) rates in patients with breast cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX) has been reported as highly effective and less toxic compared with Cremophor-based Taxol. This phase II clinical trial evaluated the safety and efficacy of preoperative neoadjuvant chemotherapy (NAC) with nab-PTX followed by an epirubicin plus cyclophosphamide (EC)-based regimen for operable breast cancer.Patients and methodsFrom June 2012 to January 2014, four cycles of every-3-week (q3w) nab-PTX [plus q3w trastuzumab in cases of human epidermal growth factor 2 (HER2) positivity] followed by four cycles of q3w EC were administered to patients with operable breast cancer (stage IC–IIIA). The primary endpoint was the pCR rate (ypT0/TisypN0).ResultsA total of 55 patients were enrolled, 54 of whom received at least one nab-PTX dose. All patients underwent radical surgery after chemotherapy. The overall pCR rate was 22.2% (p = 0.006). The pCR rates for patients with the luminal B, luminal/HER2, HER2-rich, and triple-negative breast cancer subtypes were 10.5, 29.4, 60, and 15.4%, respectively. Stepwise logistic regression analysis revealed only HER2 as a significant factor for pCR (odds ratio 5.603; p = 0.024). The expression of secreted protein acidic and rich in cysteine showed no association with pCR. The clinical response rate was 70.4% (38/54), and the safety profile was tolerable.ConclusionPreoperative NAC with nab-PTX followed by EC is effective and safe for operable breast cancer.

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An intractable fistula caused by idiopathic esophageal rupture is a rare but severe condition. In the present case, a 69‐year‐old man had been treated conservatively at another hospital for esophageal rupture but had developed an abscess in the left thoracic cavity due to an intractable fistula at the rupture site. He was referred to our hospital for treatment 19 months after the esophageal rupture. On admission, the intractable fistula was found to be continuous with an abscess in the left thoracic cavity. Preoperative continuous enteral nutrition was administered to improve the patient's nutritional status, and drainage was performed to reduce the size of the abscess. Then, to minimize the invasion of the intractable fistula, thoracoscopic subtotal esophagectomy was performed via a right thoracic cavity approach 20 months after the esophageal rupture. Preoperative management and thoracoscopic surgery via an opposite chest cavity approach was found to be safe and feasible for the intractable fistula caused by idiopathic esophageal rupture.