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Futoshi Muranaka

Bio: Futoshi Muranaka is an academic researcher from Shinshu University. The author has contributed to research in topics: Medicine & Cancer. The author has an hindex of 3, co-authored 18 publications receiving 77 citations.
Topics: Medicine, Cancer, Panitumumab, Cetuximab, Trametinib

Papers
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Journal ArticleDOI
TL;DR: AMM patients treated by curative surgery can expect long-term survival, although the usefulness of adjuvant chemotherapy for AMM patients is controversial.
Abstract: Introduction Anorectal malignant melanoma (AMM) is a relatively rare disease. Because of its poor prognosis, the optimal surgical treatment for AMM is still controversial and difficult to determine. In this paper, we report five cases of AMM that have been treated by surgery and/or other methods at Shinshu University Hospital within the last decade. We also review the present five cases along with 74 other Japanese cases reported between 1997 and 2006 and discuss the role of surgery in the treatment of AMM.

70 citations

Journal ArticleDOI
TL;DR: The MUC5AC+/SOX2+/M UC5AC−/MUC2−/CDX2− /CDx2− profile of the ATZ epithelium and anal glands is a useful feature for diagnosing adenocarcinoma arising from these regions.
Abstract: To better understand the cellular origins and differentiation of anal canal epithelial neoplasms, the immunohistochemical profiles of the anal canal epithelium in humans and swine were evaluated. Formalin-fixed tissue sections were immunostained for mucin (MUC: MUC2, MUC5AC, MUC5B), desmoglein 3 (DGS3), p63, CDX2, SOX2, and α-smooth muscle actin (α-SMA). The anal transitional zone (ATZ) epithelium covered the anal sinus and consisted of a stratified epithelium with mucous cells interspersed within the surface lining. Anal glands opened into the anal sinus. Ducts and acini of intraepithelial or periepithelial mucous type were the main structures of human anal glands, whereas those of swine were compound tubuloacinar mixed glands. Distal to the ATZ epithelium, non-keratinized stratified squamous epithelium merged with the keratinized stratified squamous epithelium of the perianal skin. MUC5AC expression predominated over MUC5B expression in the ATZ epithelium, while MUC5B expression was higher in the anal glands. SOX2 was positive in the ATZ epithelium, anal glands, and squamous epithelium except in the perianal skin. In humans, DGS3 was expressed in the ATZ epithelium, anal gland ducts, and squamous epithelium. p63 was detected in the ATZ epithelium, anal glands, and squamous epithelium. Myoepithelial cells positive for α-SMA and p63 were present in the anal glands of swine. Colorectal columnar cells were MUC5B+ /MUC2+ /CDX2+ /MUC5AC- /SOX2- . The ATZ epithelium seems to be a distinctive epithelium, with morphological and functional features allowing smooth defecation. The MUC5AC+ /SOX2+ /MUC2- /CDX2- profile of the ATZ epithelium and anal glands is a useful feature for diagnosing adenocarcinoma arising from these regions. Anat Rec, 301:796-805, 2018. © 2017 Wiley Periodicals, Inc.

10 citations

Journal ArticleDOI
01 Jan 2021-Oncology
TL;DR: In this article, the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer was analyzed.
Abstract: Introduction Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. Methods In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. Results Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (p = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; p = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; p = 0.022). Conclusions Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.

6 citations

Journal ArticleDOI
TL;DR: In patients with suspected pseudo-Meigs' syndrome secondary to ovarian metastasis of colorectal cancer, operation including oophorectomy may reduce pleural effusions and/or ascites and improve the general condition.
Abstract: Pseudo-Meigs' syndrome is used to describe cases of ascites and/or pleural effusion associated with ovarian neoplasms other than benign tumors, which improve after removal of the ovarian lesion. We present three cases of pseudo-Meigs' syndrome secondary to ovarian metastasis from colorectal cancer. In case 1, the patient has severe dyspnea and hypoxia due to massive right pleural effusion; therefore preoperative thoracic drainage was needed. In case 2, the patient needed paracentesis every two or three days to improve abdominal distension. After two courses of 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6), her ascites could be controlled by diuretics without aspiration and her general condition improved. Then she underwent operation. In case 3, the patient developed a massive pleural effusion and ascites coincident with a rapid enlargement of ovarian tumor after resection and adjuvant chemotherapy for rectal cancer. In all cases, pleural effusions and/or ascites resolved and general conditions and daily activities of the patients improved after oophorectomy. They are all currently in good health without recurrence of pleural effusion or ascites. In patients with suspected pseudo-Meigs' syndrome secondary to ovarian metastasis of colorectal cancer, operation including oophorectomy may reduce pleural effusions and/or ascites and improve the general condition.

5 citations

Journal ArticleDOI
TL;DR: It is suggested that a low dose of trametinib (10 nM), rather than the usual dose of 100–nM, in combination with ABT263 can overcome the resistance to apoptosis induced by Bcl‑xL expression, which occurs concurrently with p‑ERK suppression in KRAS‑mutant cells.
Abstract: KRAS‑mutant colorectal cancer (CRC) is a highly malignant cancer with a poor prognosis, however specific therapies targeting KRAS mutations do not yet exist. Anti‑epidermal growth factor receptor (EGFR) agents, including cetuximab and panitumumab, are effective for the treatment of certain patients with CRC. However, these anti‑EGFR treatments have no effect on KRAS‑mutant CRC. Therefore, new therapeutic strategies targeting KRAS‑mutant CRC are urgently needed. To clarify the direct effect of KRAS gene mutations, the present study transduced mutant forms of the KRAS gene (G12D, G12V and G13D) into CACO‑2 cells. A drug‑screening system (Mix Culture assay) was then applied, revealing that the cells were most sensitive to the MEK inhibitor trametinib among tested drugs, Cetuximab, Panitumumab, Regorafenib, Vemurafenib, BEZ‑235 and Palbociclib. Trametinib suppressed phosphorylated ERK (p‑ERK) expression and inhibited the proliferation of KRAS‑mutant CACO‑2 cells. However, low‑dose treatment with trametinib also increased the expression of the anti‑apoptotic protein Bcl‑xL in a dose‑dependent manner, leading to drug resistance. To overcome the resistance of KRAS‑mutant CRC to apoptosis, the combination of trametinib and the Bcl‑xL antagonist ABT263 was assessed by in vitro and in vivo experiments. Compared with the effects of low‑dose trametinib monotherapy, combination treatment with ABT263 had a synergistic effect on apoptosis in mutant KRAS transductants in vitro. Furthermore, in vivo combination therapy using low‑dose trametinib and ABT263 against a KRAS‑mutant (G12V) xenograft synergistically suppressed growth, with an increase in apoptosis compared with the effects of trametinib monotherapy. These data suggest that a low dose of trametinib (10 nM), rather than the usual dose of 100 nM, in combination with ABT263 can overcome the resistance to apoptosis induced by Bcl‑xL expression, which occurs concurrently with p‑ERK suppression in KRAS‑mutant cells. This strategy may represent a promising new approach for treating KRAS‑mutant CRC.

4 citations


Cited by
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Journal ArticleDOI
TL;DR: The history and current status of management of anorectal melanoma is reviewed, with a particular focus on surgical controversies and challenges in optimizing survival.
Abstract: An increase in the incidence of anorectal melanoma has recently been noted in the United States. Anorectal melanoma is an uncommon and lethal condition, with a median survival of <20 months. Unfortunately, nonspecific symptoms also attributable to common and benign conditions (eg, hemorrhoids) cause significant delay in its diagnosis. Although it has not been validated by clinical trials, abdominoperineal resection has historically been the treatment of choice for this disease. However, for the past 2 decades, a lack of clear survival benefit has led to a shift toward less-mutilating wide local excisions. Controversy still exists regarding the benefit of radiation therapy and chemotherapy. Furthermore, the value of nodal surgery in anorectal melanoma is unclear. In this article, we review the history and current status of management of anorectal melanoma, with a particular focus on surgical controversies and challenges in optimizing survival.

64 citations

Journal ArticleDOI
TL;DR: A large series analyzing 85,000 patients with melanoma showed that mucocutaneous melanoma was found in 1.3% only and 24% of these were ARMMs.
Abstract: The first case of anorectal malignant melanoma (ARMM) was reported by Moore in 1857. Anorectal malignant melanoma is an extremely rare malignancy and represents only 0.05% of all malignant colorectal neoplasms and 0.5% to 4.6% of all malignant anorectal cancers that have been described. Up to 67% of patients are found to have distant metastases at the time of initial presentation, which is associated with extremely poor prognosis and median overall survival between 8.0 and 18.6 months. A large series analyzing 85,000 patients with melanoma showed that mucocutaneous melanoma was found in 1.3% only and 24% of these were ARMMs. Highly experienced cancer centers generally treat no

59 citations

Journal ArticleDOI
TL;DR: It is suggested that APR has no survival benefit; however, APR confers better local control than LE, given that local failures after LE could be managed by salvage surgery, minimizing morbidity and maximizing quality of life should be the focus in surgical treatment of ARMM.
Abstract: Objective:To determine whether the extent of surgery is associated with survival in anorectal malignant melanoma (ARMM).Background:ARMM is a rare and highly malignant neoplasm with unfavorable prognosis. The optimal surgical management, abdominoperineal resection (APR) or local excision (LE), has be

56 citations

01 Jan 2013

45 citations

Journal ArticleDOI
TL;DR: Complete or R0 resection is the first choice of treatment for anorectal melanoma, prognosis is poor regardless of surgical approach, and early diagnosis is the key to improved survival rate for patients with anorectic melanoma.
Abstract: AIM: To present the experience and outcomes of the surgical treatment for the patients with anorectal melanoma from the Cancer Hospital, Chinese Academy of Medical Sciences. METHODS: Medical records of the diagnosis, surgery, and follow-up of 56 patients with anorectal melanoma who underwent surgery between 1975 and 2008 were retrospectively reviewed. The factors predictive for the survival rate of these patients were identified using multivariate analysis. RESULTS: The 5-year survival rate of the 56 patients with anorectal melanoma was 20%, 36 patients underwent abdominoperineal resection (APR) and 20 patients underwent wide local excision (WLE). The rates of local recurrence of the APR and WLE groups were 16.13% (5/36) and 68.75% (13/20), (P = 0.001), and the median survival time was 22 mo and 21 mo, respectively (P = 0.481). Univariate survival analysis demonstrated that the number of tumor and the depth of invasion had significant effects on the survival (P < 0.05). Multivariate analysis showed that the number of tumor [P = 0.017, 95% confidence interval (CI) = 1.273-11.075] and the depth of invasion (P = 0.015, 95% CI = 1.249-7.591) were independent prognostic factors influencing the survival rate. CONCLUSION: Complete or R0 resection is the first choice of treatment for anorectal melanoma, prognosis is poor regardless of surgical approach, and early diagnosis is the key to improved survival rate for patients with anorectal melanoma.

38 citations