Targeting N-cadherin increases vascular permeability and differentially activates AKT in melanoma.

Objective: We investigate the mechanism through which N-cadherin disruption alters the effectiveness of regional chemotherapy for locally advanced melanoma.

Background: N-cadherin antagonism during regional chemotherapy has demonstrated variable treatment effects.

Methods: Isolated limb infusion (ILI) with melphalan (LPAM) or temozolomide (TMZ) was performed on rats bearing melanoma xenografts after systemic administration of the N-cadherin antagonist, ADH-1, or saline.

[A case of mucosa-associated lymphoid tissue lymphoma of the rectum].

We report a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum in a 67-year-old woman who was admitted to our hospital owing to bowel abnormalities. Colonoscopic examination revealed a submucosal tumor (SMT) in the lower rectum. However, no malignancy was found on rectal mucosa biopsy.

[A case of pelvic recurrence of rectal cancer successfully treated by surgical resection using the extraperitoneal approach].

Here, we report a case of recurrent rectal cancer successfully treated with resective surgery using the extraperitoneal approach. A 73-year-old man underwent the Miles operation for advanced rectal cancer (Rb-P, tub1, pMP, pN0, Stage I). At 20 months after the initial operation, computed tomography( CT) and magnetic resonance imaging( MRI) scans and 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) images showed a recurrent pelvic tumor( 20 mm in diameter) located in the lower presacral region.

SRC family kinase inhibition as a novel strategy to augment melphalan-based regional chemotherapy of advanced extremity melanoma.

Background: Src kinase inhibition has been shown to augment the efficacy of chemotherapy. Dasatinib, a dual Src/Abl kinase inhibitor approved for the treatment of CML, is under investigation as monotherapy for tumors with abnormal Src signaling, such as melanoma. The goal of this study was to determine if Src kinase inhibition using dasatinib could enhance the efficacy of regionally administered melphalan in advanced extremity melanoma.

[A case of rapidly progressing anorectal malignant melanoma].

We report here a case of rapidly progressing anorectal malignant melanoma. A 66-year-old man was admitted to our hospital due to bowel abnormalities and anal pain. Detailed gastrointestinal examination revealed a nigrities-like type 1 tumor that occupied a semicircle in the intestinal lumen from the lower rectum to the anatomical anal canal.

Bevacizumab-induced alterations in vascular permeability and drug delivery: a novel approach to augment regional chemotherapy for in-transit melanoma.

Purpose: To investigate whether the systemically administered anti-VEGF monoclonal antibody bevacizumab could improve regional chemotherapy treatment of advanced extremity melanoma by enhancing delivery and tumor uptake of regionally infused melphalan (LPAM).

Experimental Design: After treatment with systemic bevacizumab or saline, changes in vascular permeability were determined by spectrophotometric analysis of tumors infused with Evan's blue dye. Changes in vascular structure and tumor hemoglobin-oxygen saturation HbO(2) were determined by intravital microscopy and diffuse reflectance spectroscopy, respectively.

[A case of rectal cancer with interstitial pneumonia successfully treated with preoperative radiation therapy].

We report here a case of rectal cancer with interstitial pneumonia was successfully treated with preoperative radiation therapy. An 81-year-old man with complaints of constipation and melena was admitted to our hospital for the purpose of close inspection and medical treatment. In colonoscopic examination, we found a type-3 9 cm tumor in mainly occupied lower rectum (Rb), which developed all circumference-related stenosis.

[A case of rectal cancer with synchronous multiple liver metastases successfully treated with combined chemotherapy of modified FOLFOX6 and bevacizumab].

We report here a case of rectal cancer with synchronous multiple liver metastases successfully treated with a combined chemotherapy of modified FOLFOX6 (mFOLFOX6) and bevacizumab. A 49-year-old man was admitted to our hospital due to constipation and anorexia. Abdominal ultrasonography and abdominal computed tomography (CT) scan revealed a rectal tumor (Rs) and abdominal abscess and 11 mm hepatic nodular lesion in S3 and 21 mm and 14 mm hepatic nodular lesions in S4.

[A case of recurrent esophageal cancer successfully treated by combined therapies].

We report here a case of recurrent esophageal cancer successfully treated by cervical lymph node dissection and chemo-radiation therapy. A 66-year-old woman received esophagectomy for advanced esophageal cancer in February 2003. Cervical CT and ultrasonography revealed multiple lymph node metastases in February 2008.

Sorafenib, a multikinase inhibitor, enhances the response of melanoma to regional chemotherapy.

Melanoma responds poorly to standard chemotherapy due to its intrinsic chemoresistance. Multiple genetic and molecular defects, including an activating mutation in the BRaf kinase gene, are associated with melanoma, and the resulting alterations in signal transduction pathways regulating proliferation and apoptosis are thought to contribute to its chemoresistance. Sorafenib, a multikinase inhibitor that targets BRaf kinase, is Food and Drug Administration approved for use in advanced renal cell and hepatocellular carcinomas.

Inhibition of poly(ADP-ribose) polymerase enhances the effect of chemotherapy in an animal model of regional therapy for the treatment of advanced extremity malignant melanoma.

Background: Poly(ADP-ribose) polymerase (PARP) is an important regulator of programmed cell death in response to alkylating agents such as temozolomide (TMZ). The goal of this study was to determine if a systemically administered PARP-inhibitor (INO-1001) could augment the efficacy of TMZ in a rat model of extremity malignant melanoma.

Materials And Methods: PARP activity was measured in vitro across a panel of 5 human malignant melanoma-derived cell lines.

Molecular features linked to the growth-inhibitory effects of gemcitabine on human pancreatic cancer cells.

Although gemcitabine (GEM) is widely used in the treatment of pancreatic cancers, the molecular mechanisms that underlie its anti-tumor effects are not fully understood. To clarify the anti-tumor mechanism(s) of GEM, we studied a human pancreatic cancer cell line, YPK-1, that showed a 50% inhibitory concentration (IC50) of GEM of 6.3 x 10(-3) microg/ml after 72 h of exposure.

[A resected case of effective treatment with TS-1 and CDDP for advanced gastric cancer with carcinomatous ascites].

We encountered a resected case of advanced gastric cancer after successful chemotherapy. The patient remained alive in good condition without any signs of recurrence at 2 years and 8 months after surgery. The 40-year-old woman initially complained of low abdominal pain, which was diagnosed as gastric cancer with metastasis of ovaries and carcinomatous ascites.

Molecular signature linked to acquired resistance to cisplatin in esophageal cancer cells.

To clarify the molecular basis of acquired cisplatin (CDDP) resistance in esophageal squamous cell carcinoma (ESCC), we used cDNA microarray technology. A CDDP-resistant cell line (YES-2/CDDP), which shows a 7.5-fold increase in resistance to CDDP and a 3-fold decrease in CDDP accumulation compared with the parental YES-2 ESCC cell line, was generated from YES-2 by exposure to increased concentrations of CDDP.

Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma.

Purpose: Selection of appropriate protocols for treatment of superficial esophageal squamous cell carcinoma (SESCC) is dependent on lymph node metastasis status. Therefore, it is important to know whether lymph node metastasis is present before treatment.

Experimental Design: In this study, we examined the relation between DNA sequence copy number aberrations detected by comparative genomic hybridization and lymph node metastasis in 26 surgically resected SESCCs (training samples).

Gain of 5p15 detected by comparative genomic hybridization as an independent marker of poor prognosis in patients with esophageal squamous cell carcinoma.

Comparative genomic hybridization was applied to 51 primary esophageal squamous cell carcinomas (ESCCs) to clarify the relation between DNA sequence copy number aberrations (DSCNAs) and the clinicopathology of the disease. The average number of DSCNAs was 10.9 DSCNAs/tumor (6.