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S Saji

Publications and source records attributed to S Saji.

At least 19 recordsLinked to original sources
PubMed2026

Eribulin versus taxane as first-line chemotherapy combined with dual HER2 blockade in patients with HER2-positive locally advanced or metastatic breast cancer: final survival outcomes of the JBCRG-M06/EMERALD study.

BACKGROUND: The phase III JBCRG-M06/EMERALD study was the first to show noninferior progression-free survival (PFS) of eribulin to taxane, combined with dual human epidermal growth factor receptor 2 (HER2) blockade (trastuzumab plus pertuzumab), as a first-line treatment for HER2-positive locally advanced breast cancer or metastatic breast cancer (LABC/MBC). We report final survival outcomes and biomarker analyses of the EMERALD trial. PATIENTS AND METHODS: Patients with HER2-positive LABC/MBC were randomly assigned 1:1 to either eribulin or physician-choice taxane (docetaxel or paclitaxel), both combined with trastuzumab plus pertuzumab, as first-line chemotherapy. PFS and overall survival (OS) were assessed through 30 June 2023 for PFS and 31 December 2024 for OS. Survival outcomes were compared between the eribulin and taxane groups and according to circulating tumor DNA (ctDNA) detection of PIK3CA mutations (PIK3CAm+; E542K, E545K, H1047R, and N345K single nucleotide variants) or HER2 amplification (HER2 amp+; ERBB2 copy number >2.5). RESULTS: Median OS was 78.5 months [95% confidence interval (CI) 64.3-not reached (NR)] for eribulin and was NR for taxane, with a hazard ratio of 1.25 (95% CI 0.92-1.71, log-rank P = 0.19). The 60-month OS rates were 59.7% and 65.2% for eribulin and taxane, respectively. Median OS and 60-month OS rates were numerically lower in ctDNA PIK3CAm+ patients, and greater in ctDNA HER2 amp+ patients for all patients and with stratification by treatment group. There were no statistical interactions between treatment group with either ctDNA PIK3CAm or ctDNA HER2 amp status. Similar patterns were observed for PFS. CONCLUSION: Final survival analysis revealed that median OS exceeded 6 years with eribulin or physician-choice taxane, combined with trastuzumab plus pertuzumab, as first-line chemotherapy for HER2-positive LABC/MBC, with no significant differences between the two groups. ctDNA PIK3CAm+ status was a poor prognostic factor. ctDNA HER2 amp+ was associated with longer survival.

Aged↗
PubMed2006

A case of a large retroperitoneal liposarcoma presenting as an incarcerated inguinal hernia.

We report a rare case of retroperitoneal liposarcoma developing within an incarcerated inguinal hernia. A 53-year-old man presented to our hospital with left inguinal mass. Preoperative computed tomography revealed an intraabdominal huge mass, and a clinical diagnosis of liposarcoma. Physical findings except for the inguinal mass and laboratory examination, including tumor markers (CEA, CA19-9), were within normal range. Intraoperatively, the mass was incarcerated in the inguinal canal and involved the left testis. We performed a radical tumor resection, including a left orchiectomy. The resected specimen measured 45 x 30 cm and weighed 7,510 g. Histopathologically, the tumor was diagnosed as a well-differentiated liposarcoma, and originated from retroperitoneum. We did not undergo adjuvant therapy in consideration of histopathological subtype and curable surgical treatment. The patient is well and shows no evidence of recurrence four months after the operation.

Drainage↗
PubMed2004

Modulation of thymidine phosphorylase by neoadjuvant chemotherapy in primary breast cancer.

The combination effect of docetaxel and capecitabine on tumour response rate and survival was demonstrated recently in metastatic breast cancer patients. This combination was based on an experimental hypothesis that taxane can increase tumour sensitivity to the effect of capecitabine through the upregulation of thymidine phosphorylase (TP), which is responsible for the metabolism of 5-fluorouracil (5-FU) and its derivatives, including capecitabine. To examine the alteration in TP expression before and after neoadjuvant chemotherapy, 92 patients with primary breast cancer (T2-4N0-1M0) were enrolled in this study; 14 were treated with adriamycin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC); 58 with 5-FU, adriamycin, and cyclophosphamide (FAC) or 5-FU, epirubicin, and cyclophosphamide (FEC); and 20 with FEC followed by docetaxel/taxotere (TXT-containing regimen). Thymidine phosphorylase upregulation was seen in 54.4% and 32.6% of patients in tumour cells and stromal cells, respectively. Increases in TP expression were found only in the AC/EC and TXT-containing regimen groups. In conclusion, it was strongly suggested that unlike 5-FU-containing regimens, the taxane and AC combination therapies upregulate TP expression in primary breast cancer. Thymidine phosphorylase upregulation by several anticancer drugs implies the importance of individualised strategies for sensitisation of tumour tissues to 5-FU and its derivatives.

Adult↗
PubMed2004

The expression of oestrogen receptor (ER)-beta and its variants, but not ERalpha, in adult human mammary fibroblasts.

Whilst oestrogen receptor (ER)-alpha and ERbeta have been shown to be important in the development of the mammary gland, the cell-specific expression pattern of these two receptors within the human breast is not clear. Although it is well established that in the developing rodent mammary gland stromal ERalpha mediates the secretion of growth factors which stimulate the proliferation of the ductal epithelium, the expression of ERalpha in human adult breast stromal fibroblasts is controversial, and the expression of ERbeta has not been properly defined. In the present study, we have evaluated the expression of ERalpha and ERbeta by immunohistochemistry in normal tissue samples, and in purified human breast fibroblasts by Western blotting, RT-PCR analysis and ligand-binding sucrose gradient assay. Our data clearly demonstrated that ERbeta variants, including ERbeta1, ERbeta2, ERbeta5, ERbetadelta and ERbetains, but not ERalpha, are expressed in human adult mammary fibroblasts. These results are supported by the findings that an ERbeta-selective ligand, BAG, but not the ERalpha high-affinity ligand oestradiol, can induce fibroblast growth factor-7 release and activate transcription from an oestrogen-responsive element promoter in these adult human mammary fibroblasts. Together, these observations revealed that, in the adult breast and in breast cancer, the proliferative signals derived from the stroma of adult mammary glands in response to oestrogen are not mediated by ERalpha and provide new insights into the nature of stromal-epithelial interactions in the adult mammary gland. In addition, the expression of these ERbeta variants in cells where there is no ERalpha suggested that these ERbeta splice forms may have functions other than that of modulating ERalpha activity.

Animals↗
PubMed2002

Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial.

BACKGROUND: The purpose of this study is to evaluate the efficacy of postoperative adjuvant chemotherapy using uracil and tegafur (UFT) for colorectal cancer. METHODS: In a multicenter trial among 43 institutions for patients who underwent curative resection of Dukes' B or C colorectal cancer, a surgery alone group (control group) and a treatment group (UFT group) to which UFT was administered at 400 mg/day for 2 years following surgery were compared. A total of 320 patients were registered between March 1991 and April 1994, and 289 of these patients were analyzed as a full-analysis set. RESULTS: The 5-year disease-free survival rate was 75.7% in the UFT group and 60.1% in the control group, respectively, and the stratified log-rank test showed the statistical significance ( P=0.0081). This difference was marked in rectal cancer ( P=0.0016) and, in particular, the local recurrence was reduced. No significant difference was observed in the 5-year survival rate. The incidence of adverse reactions on administration of UFT was low, and there was no serious adverse reaction. CONCLUSION: It is suggested that the consecutive administration of UFT at 400 mg/day was an effective and highly safe therapeutic method as postoperative adjuvant chemotherapy for rectal cancer.

Adenocarcinoma↗
PubMed2002

Estrogen receptor beta in breast cancer.

Estrogen is essential for normal growth and differentiation in the mammary gland. It also supports growth of approximately 50% of primary breast cancers. For this reason, removal of estrogen or blocking of its action with the anti-estrogen, tamoxifen, is the main treatment for estrogen receptor alpha (ERalpha)-positive tumors. In 1996, when oncologists became aware of a second ER, ERbeta, there was some doubt as to whether this receptor would be of importance in breast cancer because the clinical consensus was that responsiveness to tamoxifen is related to the presence of ERalpha in breast cancer. Today we know that ERalpha and ERbeta have distinct cellular distributions, regulate separate sets of genes and can oppose each other's actions on some genes. We also know that ERbeta is widely expressed in both the normal and malignant breast and that there are proliferating cells in the breast which express ERbeta. In this review we summarize what is known about ERbeta in breast cancer and examine the possibility that ERbeta-selective ligands may well represent a useful class of pharmacological tools with a novel target, namely proliferating cells expressing ERbeta.

Animals↗
PubMed2002

Detection of peritoneal micrometastases by reverse transcriptase-polymerase chain reaction targeting carcinoembryonic antigen and cytokeratin 20 in colon cancer patients.

Peritoneal recurrence after curative resection of malignant tumor with negative cytology is considered to be caused by microscopic dissemination of the exfoliated cancer cells from primary tumors to serosal surfaces at the time of operation, not detectable with conventional diagnostic tools. We applied the reverse transcriptase-polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK 20) to detect micrometastatic foci in the peritoneal cavity of colon cancer patients. Cytological samples taken by peritoneal lavage from a series of 79 colon cancer patients were analyzed microscopically, for CEA levels, and by RT-PCR analysis using nested primers for CEA and CK 20. Cases with both CEA and CK 20 signals were defined as PCR-positive. This RT-PCR method proved both sensitive (1 tumor cell/10(6) non-tumor cells on preparation of serial colorectal cancer cell dilutions) and specific (no false positive results, 0/23 tested in our control experiment). Intraperitoneal micrometastatic cells were detected in peritoneal lavage 7.6% by cytology, 17.7% by CEA levels, and 24.1% by RT-PCR (significantly higher than by cytology: p=0.0046). RT-PCR detection rate increased in parallel with pathological depth of tumor invasion, and also a pathological stage-dependence was suggested according to the tumor-node-metastasis classification of the International Union Against Cancer. Our results suggest that CEA and CK 20 mRNA identification by RT-PCR appeared to be reliable and may be useful for early diagnosis in peritoneal dissemination of colon cancer.

Aged↗
PubMed2001

Estrogen receptors and proliferation markers in primary and recurrent breast cancer.

To elucidate the clinical importance of estrogen receptor (ER) beta in breast cancer, 29 archival primary breast cancer specimens, six locally recurrent cancers, and five benign mammary tumors were examined histochemically for ERalpha, ERbeta and the proliferation markers Ki67 and cyclin A. In benign tumors, most epithelial cells contained ERbeta, but ERalpha was rare. In primary cancers, both ERalpha and ERbeta occurred in epithelial cells, the presence of ERbeta being associated with elevated expression of Ki67 and cyclin A, and ERalpha with decreased levels. Thus, the highest content of proliferation markers was seen in primary cancers that were ERalpha(-) ERbeta(+). Most Ki67-containing cells coexpressed ERbeta, but few showed ERalpha. In locally recurring cancers, ERalpha, ERbeta, and Ki67 were more highly expressed than in the corresponding primary tumors, and many cells containing ERbeta, but few with ERalpha, expressed Ki67. Surprisingly, ERbeta, but not ERalpha, was seen in the stromal cells of both primary and recurrent cancers. Because the response of breast cancers to tamoxifen therapy is correlated with the presence of ERalpha, cancer cells that lack ERalpha but contain ERbeta and proliferation markers represent a novel population of apparently proliferating cells that probably are not targeted by the current antiestrogens. Thus, appropriate ERbeta-specific ligands, perhaps in combination with tamoxifen, may be useful in improving the treatment of breast cancers.

Biomarkers, Tumor↗
PubMed2001

Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma.

BACKGROUND: Macrophages often infiltrate into solid tumor tissues. Tumor-associated macrophages (TAMs) are known to play a crucial role in tumor progression. Monocyte chemoattractant protein-1 (MCP-1) is one of the major chemokines capable of inducing chemotactic migration of monocytes. METHODS: With the objective of investigating the clinical significance of MCP-1, the authors analyzed the expression of MCP-1 and of some other molecules by immunohistochemistry in 230 samples of primary breast carcinoma tissue. MCP-1 staining was performed using an anti-MCP-1 monoclonal antibody, and it was assessed by grading the percentage of stained cells. RESULTS: It was found that 117 breast tumor specimens (51%) had intensive staining in tumor cells. The expression of MCP-1 in tumor cells had a significant correlation with the expression of thymidine phosphorylase and membrane type 1-matrix metalloproteinase. In addition, MCP-1 expression tended to be associated with the accumulation of TAMs, which were counted by CD68 staining, and with microvessel density. MCP-1 expression in TAMs was correlated significantly with the histologic vessel invasion of tumor cells. CONCLUSIONS: The results of this study suggest that MCP-1 may play key roles in macrophage recruitment, in the expression of angiogenic factors, and in the activation of matrix metalloproteinases in patients with breast carcinoma.

Angiogenesis Inducing Agents↗
PubMed2001

A role for estrogen receptor beta in the regulation of growth of the ventral prostate.

In normal rats and mice, immunostaining with specific antibodies revealed that nuclei of most prostatic epithelial cells harbor estrogen receptor beta (ERbeta). In rat ventral prostate, 530- and 549-aa isoforms of the receptor were identified. These sediment in the 4S region of low-salt sucrose gradients, indicating that prostatic ERbeta does not contain the same protein chaperones that are associated with ERalpha. Estradiol (E(2)) binding and ERbeta immunoreactivity coincide on the gradient, with no indication of ERalpha. In prostates from mice in which the ERbeta gene has been inactivated (BERKO), androgen receptor (AR) levels are elevated, and the tissue contains multiple hyperplastic foci. Most epithelial cells express the proliferation antigen Ki-67. In contrast, prostatic epithelium from wild-type littermates is single layered with no hyperplasia, and very few cells express Ki-67. Rat ventral prostate contains an estrogenic component, which comigrates on HPLC with the testosterone metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol). This compound, which competes with E(2) for binding to ERbeta and elicits an estrogenic response in the aorta but not in the pituitary, decreases the AR content in prostates of wild-type mice but does not affect the elevated levels seen in ERbeta knockout (BERKO) mice. Thus ERbeta, probably as a complex with 3betaAdiol, is involved in regulating the AR content of the rodent prostate and in restraining epithelial growth. These findings suggest that ligands specific for ERbeta may be useful in the prevention and/or clinical management of prostatic hyperplasia and neoplasia.

Androstane-3,17-diol↗
PubMed2001

Critical role of extracellular signal-regulated kinase phosphorylation on menadione (vitamin K3) induced growth inhibition.

BACKGROUND: Although it is widely known that the extracellular signal-regulated kinase (ERK) pathway stimulates cell growth and protects cells from death, recent findings have proposed a proapoptotic action of ERK phosphorylation. Because the authors found that vitamin K3 (VK3) was a potent growth inhibitor and an inducer for ERK phosphorylation through a specific pathway in the stomach cancer cell line, the critical role of ERK phosphorylation in VK(3)-mediated growth inhibitory effect was examined. METHODS: The fluorochrome Hoechst 33258 assay (Hoechst AG [now Aventis] Frankfort, Germany) was used for counting cells (excitation at 360 nm; emission at 460 nm). For two-dimensional electrophoresis, cells were dissolved in urea standard buffer and applied first to isoelectronic focusing gels. Cell lysates were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using 10% polyacrylamide gels. To examine the phosphorylation of receptors, cell lysates were immunoprecipitated with receptor antibody. RESULTS: VK3 induced phosphorylation of hepatocyte growth factor receptor (c-met), epidermal growth factor receptor (EGFR), or external signal-regulated kinase (ERK), which increased progressively to a maximum level at 30 minutes, in a dose-dependent manner and occurred at growth inhibitory concentrations. VK(3)-mediated growth inhibition and protein tyrosine phosphorylation were nullified completely by glutathione or L-cysteine but not by nonthiol antioxidants, thus suggesting that sulfhydryl arylation might have been involved in VK(3)-mediated action. The phosphorylation of EGFR and c-met by VK(3) appeared to be functional, because these were coimmunoprecipitated with growth factor receptor-bound protein 2 (Grb2) and SOS1 antibody. Epidermal growth factor (EGF) or hepatocyte growth factor (HGF) stimulated increase of cyclin D1 protein after 12 hours and increased DNA content after 3 days in culture. In addition, U0126, which is a potent inhibitor for ERK phosphorylation, antagonized increase of cyclin D1, thus suggesting that EGF- or HGF-mediated ERK phosphorylation might have played an essential role for cell growth. By contrast, ERK phosphorylation by VK3 was more prolonged and intense than the signal induced by the growth factors. U0126 reduced ERK phosphorylation and prevented growth inhibition by VK3. Two-dimensional gels showed VK(3)-induced additional phospho-ERK spots, compared with those obtained from growth factors. This extra spot was completely antagonized by U0126. CONCLUSIONS: VK(3)-induced growth inhibition and protein tyrosine phosphorylation were mediated by the sulfhydryl arylation system. The tyrosine phosphorylation of EGFR or c-met by VK3 activated the Ras signaling pathway. The overexpressed ERK phosphorylation by VK3 seemed to originate from additional spots on two-dimensional gels, which played a critical role in VK(3)-induced growth inhibitory action despite the fact that ERK phosphorylation by growth factors had had an essential association with cell growth.

Apoptosis↗
PubMed2001

MDM2 enhances the function of estrogen receptor alpha in human breast cancer cells.

Overexpression of the oncoprotein MDM2, a negative feedback regulator of p53, is often observed in breast cancer tissue and cell lines, particularly in those which express estrogen receptor alpha (ERalpha). In this study, we report a novel function of MDM2, i.e., as a positive regulator of ERalpha. This function does not involve p53. MDM2 overexpressing clones derived from the breast cancer cell line, MCF-7 cells, showed a remarkable growth advantage only in estradiol supplemented conditions, and this profile coincided with increased transcriptional activity of ERalpha in these cells. Though p53 has been reported to be an inhibitor of ERalpha function, p53 protein in MDM2 overexpressing clones was more abundant than in the parental cells. When ERalpha was exogenously expressed in p53-null cells, its activity was enhanced by coexpression of MDM2. Mammalian two-hybrid assays and GST pull-down assays indicated that MDM2 could interact with ERalpha. These results indicate that MDM2 is a direct activator of ERalpha function, and suggest such a role for MDM2 in ERalpha-positive breast cancer.

Blotting, Western↗
PubMed2001

Aromatase and aromatase inhibitors.

Aromatase inhibition provides both paracrine/intracrine and endocrine treatment. Recent accumulated data clarified that 3rd generation aromatase inhibitors potently suppress intratumoral estrogen synthesis particularly in postmenopausal patients. In the 2nd-line treatment for metastatic breast cancer patients, aromatase inhibitors achieved results antitumor activity at least equal to and sometimes better than that of tamoxifen. In the first-line treatment for metastatic breast cancer patients, a recent pivotal study clearly demonstrated that aromatase inhibitor was superior to tamoxifen. Based upon these results, various adjuvant trials which compare aromatase inhibitors with tamoxifen and attempt to determine optimal combination therapies and treatment periods with aromatase inhibitors are currently being conducted. In addition, preliminary studies conducted in neoadjuvant setting indicated that aromatase inhibitors showed an extremely high response rate, which predicts a future paradigm, that neoadjuvant therapy using aromatase inhibitors singly or in combination may become standard for hormone-responsive and post-menopausal breast cancer patients.

Anastrozole↗
PubMed2001

Intrahepatic cholangiocarcinoma arising 10 years after the excision of congenital extrahepatic biliary dilation.

A 52-year-old woman was found to have a liver tumor during treatment for a liver abscess. The tumor was diagnosed as intrahepatic cholangiocarcinoma by closer examinations, including a percutaneous needle biopsy. Ten years previously, she had undergone excision of a choledochal cyst, with reconstruction by Roux-en-Y hepaticojejunostomy, as treatment for Todani's type Ia congenital biliary dilation, which had been confined only to the extrahepatic bile duct. The significant association between congenital biliary dilation and hepatobiliary malignancies is well known. Some patients have been reported to develop biliary cancer long after the excision of the entire extrahepatic bile duct and hepaticoenterostomy. However, in these patients, the development mostly took place in the remnant choledochal cyst, the anastomotic site, or in the dilated intrahepatic bile duct of Todani's type IV-A congenital biliary dilation. The development of intrahepatic cholangiocarcinoma after operation has not been reported previously in a patient with Todani's type I congenital biliary dilation. This case suggests that the entire biliary tree may have a high risk of field cancerization, even in extrahepatic congenital biliary dilation.

Bile Duct Diseases↗
PubMed2001

Usefulness of MR imaging in the postsurgical monitoring of gallbladder cancer in a patient with bile duct cancer that developed 7 years after resection of mucinous adenocarcinoma of the gallbladder.

We encountered a case of left hepatic duct cancer that developed 7 years after surgical resection of early-stage adenocarcinoma of the gallbladder. A 65-year-old woman was hospitalized with high fever and general fatigue. She also had elevated serum levels of alkaline phosphatase, gamma-glutamyltranspeptidase, and carbohydrate antigen 19-9. Seven years earlier, she had undergone extended cholecystectomy and resection of the extrahepatic bile duct for early-stage mucinous adenocarcinoma of the gallbladder. Conventional examinations did not reveal any responsible lesions. Magnetic resonance (MR) cholangiography, however, showed a tumor obstructing the left hepatic duct, and dynamic MR images revealed multiple foci of bacterial abscess in the liver. Surgically resected tissue again revealed mucinous adenocarcinoma. The present case is rare in that metachronous mucinous adenocarcinoma of the biliary system occurred after a long interval. This case suggests the usefulness of MR imaging in the postsurgical monitoring of patients with gallbladder carcinoma.

Adenocarcinoma, Mucinous↗
PubMed2001

A ruptured pancreaticoduodenal artery aneurysm associated with a splenic artery aneurysm: report of a case.

True pancreaticoduodenal artery (PDA) aneurysms are extremely rare. We report herein a case of a ruptured PDA aneurysm associated with a nonruptured splenic artery aneurysm which was successfully treated by surgery. A 55-year-old man was admitted to a local hospital complaining of sudden abdominal and back pain, and thereafter he was transferred to our university hospital. Abdominal computed tomography revealed retroperitoneal hematoma and an enhanced round spot suggesting a peripancreatic aneurysm. Emergency angiography showed a 20-mm-sized aneurysm in the inferior PDA and a 10-mm-sized aneurysm in the splenic artery. The patient underwent an emergency laparotomy with a diagnosis of a ruptured PDA aneurysm. After evacuating a large volume clot in the right retroperitoneal space and the peritoneal cavity, we detected an index finger-sized aneurysm with arterial bleeding in the right inferioposterior aspect of the pancreas. Hemostasis was obtained by oversewing the aneurysm and a ligation of the feeding arteries. A prophylactic splenectomy was performed for the nonruptured splenic artery aneurysm. This case indicates that emergency angiography is indispensable for both a definitive diagnosis and adequate surgical treatment of PDA aneurysms.

Aneurysm↗
PubMed2001

Antisense expression of a rice sucrose transporter OsSUT1 in rice (Oryza sativa L.).

We analyzed the function of a rice sucrose transporter, OsSUT1, by using antisense rice. There was no difference between antisense and wild-type plants in carbohydrate content and photosynthetic ability of the flag leaves in the vegetative growth stage, suggesting that OsSUT1 may not play an important role in carbon metabolism, at least in these materials.

Base Sequence↗