A Case of Matrix-Producing Carcinoma of the Breast.

A 61-year-old woman was referred to our hospital because of a right breast mass. A 19 mm hard mass was palpable in the A area of the right breast. A contrast-enhanced MRI showed rim enhancement at the peripheral region of the tumor, which was thought to represent the carcinoma component mainly at the periphery and the matrix component inside the tumor. A low density mass with rim enhancement at the peripheral region was observed in a contrast-enhanced CT, the same as in the MRI. Neither axillary lymph node metastasis nor distant metastasis was observed. A core needle biopsy of the tumor lead to a diagnosis of matrix-producing carcinoma (MPC). A breast-conserving mastectomy with sentinel lymph nodes biopsy was performed on the right breast MPC (T1c, N0, M0 Stage I). Histopathologically, the tumor demonstrated overt carcinoma with direct transition to a cartilaginous or osseous matrix and lacked an intervening spindle cell component. Immunohistochemistry showed estrogen receptor (ER) (-), progesterone receptor (PgR) (-), human epidermal growth factor receptor 2 (HER2) (-), and Ki67 index of 50%, so-called triple negative breast cancer. The tumor was also positive for SRY-related HMG box-9 (SOX9), which is a useful marker of chondroid differentiation in normal and neoplastic tissues. The patient lived free from recurrence for 5 years, even though her adjuvant therapy was only radiation therapy without adjuvant chemotherapy. MPC is an uncommon and relatively rare variant of metaplastic carcinoma, and the prognosis for patients with MPC is poorer than that for patients with ordinary breast cancer. Here we report a case of MPC of the breast with characteristic rim enhancement in contrast-enhanced MRI and CT. The intrinsic subtype and prognosis of MPC is controversial, and then we may need more experience with MPC cases.

Rapid postoperative reduction in prognostic nutrition index is associated with the development of pancreatic fistula following distal pancreatectomy.

BACKGROUNDS: Despite recent advances in surgical techniques and devices for pancreatic remnant closure, postoperative pancreatic fistula (POPF) still remains one of the common complications after distal pancreatectomy (DP). Identification of risk factors for POPF may lead to the development of new strategies to prevent this ominous complication. METHODS: We retrospectively reviewed data on 44 patients undergoing DP with the use of a stapler to identify risk factors for POPF. Study variables included preoperative prognostic nutritional index (PNI) and reduction rate of PNI on postoperative day (POD) 7. RESULTS: POPF occurred in 23 patients (52%), of which 13 (56%) were grade B or C. Univariate analyses comparing patients with POPF and those without POPF showed significant differences in body mass index (P = 0.0102), pancreatic thickness (P = 0.0134), white blood cell count on POD7 (P = 0.0432), C-reactive protein level on POD7 (P = 0.0123), and PNI reduction rate (P = 0.0471). A multivariate analysis revealed pancreatic thickness (P = 0.0121) and PNI reduction rate (P = 0.0165) to be significant factors for POPF. Furthermore, the PNI reduction rate was significantly higher in patients with clinically relevant (grade B/C) POPF than in those with no or grade A POPF (P = 0.0257). In most patients, the massive postoperative PNI reduction preceded the diagnosis of clinically relevant POPF. CONCLUSIONS: These findings suggest that rapid postoperative reduction in PNI is associated with the development of POPF.

Pancreatic somatostatinoma diagnosed preoperatively: report of a case.

CONTEXT: Somatostatinoma is a rare neoplasm of the pancreas. Preoperative diagnosis is often difficult. CASE REPORT: We report a 72-year-old woman with a pancreatic head tumor measuring 37 mm in diameter, and enlargement of the lymph nodes on the anterior surface of the pancreatic head and the posterior surface of the horizontal part of the duodenum. Laboratory data showed an elevated plasma somatostatin concentration. Examination of a biopsy specimen of the pancreatic head mass obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) showed histopathological features of a neuroendocrine tumor. Immunohistochemical staining showed that the tumor cells were positive for somatostatin, leading to a preoperative diagnosis of pancreatic somatostatinoma. The patient underwent pylorus-preserving pancreaticoduodenectomy. The plasma somatostatin concentration decreased progressively after surgery. CONCLUSIONS: A rare case of pancreatic somatostatinoma with lymph node metastases was presented. Immunohistochemical analysis of a biopsy specimen obtained by EUS-FNA was useful for preoperative diagnosis.

Intermittent negative pressure external drainage of the pancreatic duct reduces the incidence of postoperative pancreatic fistula after pancreaticojejunostomy.

BACKGROUND/AIMS: The formation of a pancreatic fistula remains one of the serious morbidities after pancreaticojejunostomy. This study is focused on the efficacy of negative pressure external drainage of the main pancreatic duct in pancreaticojejunostomy. METHODOLOGY: Fifty-eight consecutive patients who underwent pancreaticojejunostomy at our hospital from May 2008 to May 2012 were enrolled in this study. They were divided into a group of 25 earlier patients (Group A) with gravity drainage of the pancreatic duct (from May 2008 until May 2010) and a group of 33 later patients (Group B) with negative pressure drainage (treated from June 2010 until May 2012). These two groups were compared based on the patient characteristics, parameters related to the operation, and postoperative complications and hospital stay. Furthermore, examinations were performed for subgroups of patients with a soft pancreas (43 patients) or a hard pancreas (15 patients) based on the hardness of the remnant pancreas. RESULTS: There were no statistically significant differences between the two groups in the patient demographics, laboratory data or parameters related to the operation. Although there was no difference in the amount of drainage from the pancreaticojejunostomy, the amylase values in the drainage around the pancreaticojejunostomy of group B were significantly lower than those of group A (p = 0.026). The complication rates were also significantly lower in group B than in group A for the development of a postoperative pancreatic fistula (POPF) (p = 0.012), intraabdominal abscess (p = 0.045), or wound infection (p = 0.01). There were no statistically significant differences between the two groups in the mean hospital stay. When restricted to patients with a soft pancreas, the incidence of POPF (grade B or C) of group B was significantly lower than that of group A (p = 0.003). The P-value for the soft pancreas group was lower than that of the overall cases. In the examination restricted to patients with a hard pancreas, POPF (grade B or C) did not occur in either group. CONCLUSIONS: This retrospective study showed that the application of intermittent negative pressure external drainage of the main pancreatic duct significantly reduces the rate of pancreatic fistula and intra-abdominal abscess formation after pancreaticojejunostomy, and these effects were more remarkable in the patients with a soft pancreas.

Intestinal bleeding from arteriovenous malformations of the small bowel in a patient with Cowden syndrome: report of a case.

This report presents the case of a patient with Cowden syndrome who had arteriovenous malformations (AVMs) at the jejunum and the ileum and experienced intestinal bleeding. A 54-year-old Japanese male presented with general fatigue and melena. Endoscopic examinations showed gastrointestinal polyposis from the esophagus to the rectum. However, the site of bleeding was not identified. There were some papules on his face and neck. He also had macrocephaly and had multiple papillomas along the gum-line. These findings indicated a clinical diagnosis of Cowden syndrome. Enhanced computed tomography (CT) and angiography analyses indicated the presence of AVMs at the jejunum and the ileum. He was treated with partial resection of the jejunum and ileum including these two AVMs. This was a rare case of two AVMs involving the small bowel in a patient with Cowden syndrome. Enhanced CT was very useful and convenient for the detection of gastrointestinal AVMs in this case.

[A review of 13 cases of obturator hernia].

We reviewed clinical features of patients who we treated for obturator hernia. The subjects were 13 patients who underwent an operation for obturator hernia in our hospital between April 2002 and December 2012. The mean age was 78.5 years, and all patients were female. The mean body mass index was 16.8 kg/m(2). The Howship-Romberg sign was present in only 3 patients. All patients were correctly diagnosed by preoperative pelvic computed tomography. All patients underwent operation. Operative procedures included the laparoscopic approach in 8 patients, the open approach in 3 patients and the inguinal approach in 2 patients. The hernia hilus was repaired with a simple closure in 5 patients, and with a mesh in 8 patients. The hernia contents were small intestine in all the patients. Three patients underwent partial resection of the small intestine because of necrosis of the intestine wall. Three patients had a recurrence of the obturator hernia. In our present series, the patients with obturator hernia were slender females at an advanced age. Plevic CT was useful for the diagnosis of obturator hernia.

Efficacy of micafungin in empirical therapy of deep mycosis in surgically ill patients.

Micafungin (MCFG), an echinocandin antifungal agent, exhibits antifungal activity against Candida albicans and non-albicans Candida. The fungicidal activity of MCFG against clinical isolates of Candida species was investigated, and the clinical efficacy of MCFG in therapy of deep mycosis in surgery was studied using the AKOTT algorithm. The minimum inhibitory concentration and minimum fungicidal concentration values of fluconazole were ≤0.06-4 and >64 µg/ml, respectively, for each strain, whereas these values of MCFG were 0.008-0.5 and 0.016-1 µg/ml, suggesting that MCFG provided superior fungicidal ability against Candida albicans and non-albicans Candida. The subjects were separated into two groups: group A consisted of 20 subjects with both persisting fever refractory to broad-spectrum antibiotics and positive reaction to ß-D-glucan test, and group B consisted of 20 subjects with either of those conditions. The overall response was evaluated as "effective" in 17 patients (85%) and 20 patients (100%) in groups A and B, respectively. In total, response was evaluated as "effective" in 37 patients (92.5%) and "ineffective" in 3 patients (7.5%). These findings suggest that MCFG administration should be used as empirical therapy for deep mycosis in surgically ill patients as it was shown to be an effective antifungal drug lacking serious adverse effects.

[Serous cystadenoma of the pancreas showing enlargement on images: a case report].

Serious Cystadenoma (SCA) of the Pancreas is seldom malignant and is usually monitored over time. Here we report a case of SCA an enlarged cyst that had to be excised because it was difficult to diagnose by intraductal papillary-mucinous neoplasm (IPMN). The patient was a 58-year-old woman with thecoma of the right ovary accompanied by Meigs syndrome, who had undergone abdominal total hysterectomy and bilateral oophorectomy. Abdominal computed tomography scan (CT) showed a multilocular cyst 2.4 cm in diameter in the head of the pancreas. Fourteen months later, a periodic CT showed that the multilocular cyst had enlarged from 2.4 to 3.5 cm in diameter. Branch duct intraductal papillary-mucinous neoplasm (IPMN) with a tendency to enlargement and with mural nodule was suspected. Pylorus-preserving pancreatoduodenectomy (PPPD) was performed, and pathological findings revealed that the cyst was lined with a single layer of simple cuboidal epithelium. Periodic acid-Shiff staining, with and without diastase digestion, showed abundant glycogen within epithelial cells, yielding a definitive diagnosis of SCA. The ascites were probably due to the Meigs syndrome pressing the cyst, and the size of the cyst appeared smaller than the real size.

Malignant fibrous histiocytoma originating from the mesorectum: a case report.

BACKGROUND: Malignant fibrous histiocytoma (MFH) is a common sarcoma affecting soft tissues of the body, especially of the extremities or trunk. Prognosis of the abdominal MFH is usually poor. CASE PRESENTATION: A 52-year-old female presented to our surgical outpatient clinic with a lower abdominal tumor that had been gradually increasing in size. Clinical examination revealed a firm, irregularly surfaced, fixed, painless, child-head-sized tumor located in her lower abdomen. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed a polycystic tumor at the lower abdomen which was 15 × 13 × 11 cm in diameter and encased the colorectum to the left back side. A barium enema and a colonoscopy showed direct invasion to the rectum. In 2001, the tumor had been excised along with a low anterior resection of the rectum because of direct invasion. The origin of this tumor was the mesorectum. The weight of the excised tumor was 1,500 g, including 800 ml of a brown fluid. A histopathological diagnosis revealed a common type of MFH, in which mitotic figures are frequently seen. CONCLUSION: This patient has survived without recurrence, for approximately 8 years since the completed tumor resection. It is important to obtain a complete resection during the MFH treatment.

Enucleation of an Insulinoma of the Pancreas Using Reduced Port Surgery: Report of a Case.

Reduced port surgery (RPS) is a new surgical modality producing increased cosmetic benefits over conventional endoscopic surgery. We herein report the first case of insulinoma of the pancreas treated by RPS. RPS enucleation was performed for a 23-year-old Japanese female who was admitted to our hospital with repeated episodes of hypoglycemia attributable to an insulinoma. The preoperative examinations confirmed the diagnosis of a solitary insulinoma of the pancreatic tail. Enucleation of the insulinoma using RPS was performed. A 2.5-cm umbilical incision was made, and three laparoscopic trocars were individually inserted into the abdominal cavity via this incision. Another 3-mm trocar was inserted from the left subcostal region. All procedures that were usually performed in conventional laparoscopic surgery were also performed by RPS: intraoperative ultrasonography, mobilization of the tail of the pancreas, enucleation of the tumor, and suturing of the stump. A mechanical manipulator, the Radius Surgical System (Radius), was used for suturing and ligation. The Radius was sufficient to overcome in-line viewing and hand/instrument collisions, and enabled us to perform precise suturing and ligation. Serial blood sugar, C-peptide immunoreactivity (CPR), and immunoreactive insulin (IRI) measurements revealed that all values were normal after resection. The patient had an uneventful postoperative course. RPS was successfully applied for enucleation of a solitary mass in the tail of the pancreas, and represents an alternative to conventional laparoscopic surgery. This method is technically feasible and results in superior cosmesis. The Radius facilitated advanced laparoscopic surgery and may also have advantages in RPS.

[A case of sigmoid colon cancer with peritoneal dissemination responding to third-line therapy employing bevacizumab combination therapy after failure of FOLFOX and FOLFIRI].

A58 -year-old man with sigmoid colon cancer with peritoneal dissemination was treated with bevacizumab (BV) plus mFOLFOX6 therapy as third-line chemotherapy after treatment failures with FOLFOX4 and FOLFIRI regimen. BV combination therapy resulted in a decrease in ascites and disappearance of the primary lesion. His ECOG performance status (PS) recovered from level 3 to level 1, and BV combination therapy improved his quality of life. This case suggested that BV in combination with chemotherapy could be a promising systemic chemotherapy for patients with colorectal cancer with peritoneal dissemination, and this regimen may be useful for patients progressing after receiving FOLFOX, FOLFIRI regimen.

Chemopreventive effect of 4-[3,5-Bis(trimethylsilyl) benzamido] benzoic acid (TAC-101) on MNU-induced colon carcinogenesis in a rat model.

PURPOSE: 4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) is a novel retinobenzoic acid derivative. The chemopreventive effect and the mechanism of action of TAC-101 were investigated using a rat chemical colon carcinogenesis model. MATERIALS AND METHODS: Colon tumors were induced using intra-rectal instillation of N-methyl-N-nitrosourea (MNU) in F344 rats. These rats were divided into five groups, control, high dose (TAC-101 8 mg/kg)-long period (four weeks), high dose-short period (one week), low dose (TAC-101 0.8 mg/kg)-long period and low dose-short period. After the large bowels were resected at 20 weeks, the number of aberrant crypt foci (ACF) and tumors in the colon were counted. Proliferating cell nuclear antigen (PCNA) positive index, apoptotic index (AI) and Fas expression were also evaluated using immunohistochemistry. RESULTS: The tumor incidence and the tumor number in the high dose-long period group were decreased in comparison to those in the other groups, but not significantly. However, the number of ACF or PCNA positive indices in the high dose-long period group was significantly decreased in comparison to that in the other groups. On the other hand, the AI and the Fas expression pattern in the tumor and the normal appearing mucosa were not changed in any of the groups. CONCLUSION: TAC-101 might inhibit MNU induced colon carcinogenesis via a decrease of ACF. The mechanism of this chemoprevention may be related to a reduction in cell proliferation, but is not directly associated with apoptosis.

The prognostic significance of the expression of monocarboxylate transporter 4 in patients with right- or left-sided colorectal cancer.

AIM: Monocarboxylate transporter 4 (MCT4) is a proton pump that exchanges lactate through the plasma membrane. The present study investigated the clinical significance of the expression of MCT4 in patients with right- or left-sided colorectal cancer (CRC). METHODS: Surgical specimens from 237 CRC patients were immunohistochemically stained with polyclonal anti-MCT4 antibodies. The relationships among the MCT4 expression, the clinicopathological factors, and the prognosis were evaluated. RESULTS: Thirty-six (62.1%) of 58 patients with right-sided CRC and 95 (53.1%) of 179 patients with left-sided CRC showed the high expression of MCT4. The MCT4 expression was significantly correlated with gender and lymph node metastasis in patients with right-sided CRC, and size, depth of invasion, distant metastasis, and tumor-node-metastasis stage in patients with left-sided CRC. A univariate analysis demonstrated that the expression of MCT4 was a significant prognostic factor in both right- and left-sided CRC patients. A multivariate analysis demonstrated the expression of MCT4 was a significantly independent prognostic factor in patients with left-sided CRC, but not in those with right-sided CRC. CONCLUSIONS: Our results suggest that the high expression of MCT4 is a useful marker for tumor progression and a poor prognosis in CRC patients, especially those with left-sided CRC.

Cyclic AMP regulates bicarbonate secretion in cholangiocytes through release of ATP into bile.

BACKGROUND & AIMS: Bicarbonate secretion is a primary function of cholangiocytes. Either adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca(2+) can mediate bicarbonate secretion, but these are thought to act through separate pathways. We examined the role of the inositol 1,4,5-trisphosphate receptor (InsP3R) in mediating bicarbonate secretion because this is the only intracellular Ca(2+) release channel in cholangiocytes. METHODS: Intrahepatic bile duct units (IBDUs) were microdissected from rat liver then luminal pH was examined by confocal microscopy during IBDU microperfusion. Cyclic AMP was increased using forskolin or secretin, and Ca(2+) was increased using acetylcholine (ACh) or adenosine triphosphate (ATP). Apyrase was used to hydrolyze extracellular ATP, and suramin was used to block apical P2Y ATP receptors. In selected experiments, IBDUs were pretreated with short interfering RNA (siRNA) to silence expression of specific InsP3R isoforms. RESULTS: Both cAMP and Ca(2+) agonists increased luminal pH. The effect of ACh on luminal pH was reduced by siRNA for basolateral (types I and II) but not apical (type III) InsP3R isoforms. The effect of forskolin on luminal pH was reduced by a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor and by siRNA for the type III InsP3R. Luminal apyrase or suramin blocked the effects of forskolin but not ACh on luminal pH. CONCLUSIONS: Cyclic AMP-induced ductular bicarbonate secretion depends on an autocrine signaling pathway that involves CFTR, apical release of ATP, stimulation of apical nucleotide receptors, and then activation of apical, type III InsP3Rs. The primary role of CFTR in bile duct secretion may be to regulate secretion of ATP rather than to secrete chloride and/or bicarbonate.

Prognostic significance of the local expression of interleukin-12 in patients with advanced gastric cancer.

BACKGROUND: Interleukin (IL)-12 is a heterodimeric cytokine that exhibits potent antitumor and antimetastatic activities. Very few studies have so far investigated the local expression of L-12 in tumor specimens of gastric cancer. The purpose of this study was to investigate the immunohistochemical expression of IL-12 in patients with gastric cancer. PATIENTS AND METHODS: IL-12 was immunohistochemically stained using monoclonal antihuman IL-12 antibody (1-1A4) in surgical specimens of 117 gastric cancer patients. The IL-12-positive cell density was calculated. The relationships among the IL-12-positive cell density, clinicopathological factors and 5-year survival rate were evaluated. RESULTS: Among the patients (n=117), the 5-year survival rate after surgery was not statistically different between the patients with high and low IL-12 positive cell-density. However, in the patients with advanced gastric cancer (n=85), those with a high IL-12-positive cell density showed a significantly better prognosis in comparison with those with a low IL-12-positive cell density (p=0.0104). A multivariate analysis indicated that the IL-12-positive cell density and TNM stage are significant prognostic factors. CONCLUSION: IL-12-positive cell density may be a significant independent prognostic factor in surgical specimens of advanced gastric cancer.

Prognostic Significance of Mitochondrial Transcription Factor A Expression in Patients with Right- or Left-sided Colorectal Cancer.

BACKGROUND/AIM: Mitochondrial transcription factor A (mtTFA) is necessary for both the transcription and maintenance of mitochondrial DNA (mtDNA). The present study investigated the clinical significance of mtTFA in patients with right- and left-sided colorectal cancer (CRC). PATIENTS AND METHODS: Surgical specimens from 237 CRC patients were immunohistochemically stained with polyclonal anti-mtTFA antibody. The relationships among the mtTFA expression, clinicopathological factors and prognosis were evaluated. RESULTS: Thirty-five (60.3%) of 58 right-sided CRC patients and 82 (45.8%) of 179 left-sided CRC patients showed high mtTFA expression. The mtTFA expression significantly correlated with lymph node metastasis, distant metastasis, the TNM stage and lymphatic invasion in left-sided CRC patients and did not correlate with any factors in right-sided CRC patients. Univariate and multivariate analyses revealed the mtTFA expression to be a significant prognostic factor in left-sided CRC patients but not in right-sided CRC patients. CONCLUSION: These results suggest that a high mtTFA expression is a useful marker for tumor progression and a poor prognosis in left-sided CRC patients.

A novel transperitoneal abdominal wall nerve block for postoperative pain in laparoscopic colorectal surgery.

BACKGROUND: Although the laparoscopic approach reduces pain associated with abdominal surgery, postoperative pain remains a problem. Ultrasound-guided rectus sheath block and transversus abdominis plane block have become increasingly popular means of providing analgesia for laparoscopic surgery. METHODS: Ninety patients were enrolled in this study. A laparoscopic puncture needle was inserted via the port, and levobupivacaine was injected into the correct plane through the peritoneum. The patients' postoperative pain intensity was assessed using a numeric rating scale. The effects of laparoscopic nerve block versus percutaneous anesthesia were compared. RESULTS: This novel form of transperitoneal anesthesia did not jeopardize completion of the operative procedures. The percutaneous approach required more time for performance of the procedure than the transperitoneal technique. CONCLUSION: This new analgesia technique can become an optional postoperative treatment regimen for various laparoscopic abdominal surgeries. What we mainly want to suggest is that the transperitoneal approach has the advantage of a higher completion rate. A percutaneous technique is sometimes difficult with patients who have severe obesity and/or coagulation disorders. Additional studies are required to evaluate its benefits.

Significance of lymphangiogenesis as assessed by immunohistochemistry for podoplanin in patients with esophageal carcinoma.

BACKGROUND: Although lymph node involvement is an important prognostic factor for survival in patients with esophageal carcinoma, little is known about lymphangiogenesis in esophageal carcinoma. Podoplanin, a mutin-type transmembrane glycoprotein, specifically recognizes the lymphatic endothelium and is used as a lymphatic-specific marker. Anti-human podoplanin antibody was therefore used to quantify and evaluate the lymphangiogenesis in esophageal carcinoma. PATIENTS AND METHODS: Lymphatic endothelial cells were detected by immunohistochemistry using mouse monoclonal anti-human podoplanin antibody. The relationship between lymphatic microvessel density (LMVD) and lymphatic vessel invasion (LVI), clinicopathological factors and the prognosis in 29 patients with esophageal carcinoma was investigated. RESULTS: LMVD was significantly higher in esophageal carcinoma patients who had any of the following characteristics: T3-T4 (p=0.0370), tumors more advanced than stage III (TNM staging) (p=0.0351), lymphatic invasion (p=0.0095) and LVI (+) (p=0.0016). LVI significantly correlated with lymph node metastasis (p=0.0003), TNM staging (p=0.0182) and LMVD (p=0.0388). The survival rate of patients with a low LMVD tended to be higher than that of patients with a high LMVD (5-year survival rate, 62.5% vs. 29.4%, p=0.0832). CONCLUSION: The evaluation of lymphangiogenesis using podoplanin immunohistochemistry may be useful in predicting lymph node metastasis and the prognosis in patients with esophageal carcinoma.

4- [3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induced fas expression and activated caspase-3 and -8 in a DLD-1 colon cancer cell line.

BACKGROUND: 4-[3,5-Bis (trimethylsilyl) benzamido] benzoic acid (TAC-101) is a novel retinobenzoic acid derivative which has a specific binding affinity to the retinoic acid receptors (RAR)alpha and RARbeta. Using time-dependent FACScan analysis, it was observed that TAC-101 induced apoptosis in a DLD-1 human colon cancer cell line. In this study, the induction of apoptosis-related proteins and the activities of caspases in a DLD-1 cell line under medication with TAC-101 were investigated. MATERIALS AND METHODS: DLD-1 cells were cultured with different concentrations of TAC-101 for 12, 24 and 48 h. The expressions of Fas, TNF-R1, DR3, bcl-2, Bax and Bid were measured using a Western blot analysis. The activities of caspase-3, -8 and -9 were measured using a colorimetric protease assay kit. RESULTS: The Western blot analysis showed that TAC-IO1 had almost no effect on the level of Bcl-2, Bax or Bid protein. Although TAC-101 did not change the expression of TNF-R1 and DR3, TAC-101 increased the expression of Fas in both a time- and a dose-dependent manner. A 3-fold increase in caspase-3 activity and a 1.5-fold increase in caspase-8 activity were observed in cells treated with TAC-101 in comparison to the control cells (p<0.01). CONCLUSION: Our data indicate that the death receptor root of the apoptotic signal transduction in DLD-1 cells mainly participates in the apoptotic induction of TAC-101. Because the compounds inducing apoptotic activity are frequent targets of cancer therapy, TAC-101 may be a good candidate for use in the treatment of colon cancer.