Role of thrombospondin 1 (THBS1) expression in peritoneal metastasis of gastric cancer treated with taxanes.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 57-57
Author(s):  
N. Kurita ◽  
M. Shimada ◽  
T. Iwata ◽  
M. Nishioka ◽  
S. Morimoto ◽  
...  

57 Background: To clarify the utility of taxanes and to pick up the prognostic factors in the treatment with 5FU- based chemotherapy for peritoneal metastasis of gastric cancer. Methods: Responder analysis: 18 patients with peritoneal metastasis of gastric cancer were enrolled in phase I study. The regimen consists of S-1 (80-120 mg) for 14 days and intraperitoneal infusion of PTX (dose escalation: 40 - 100 mg/m2) at day 1 and 14, which was repeated 2 cycles. To pick up the predictive factors, the 137 genes, which were selected in the viewpoint of sensitivity of 5FU, CPT11 and taxanes, were analyzed using focused DNA microarray for the 12 patients. Role of THBS1 expression: THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens of 59 patients with peritoneal metastasis of gastric cancer who were administered 5FU-based chemotherapy. THBS1 positive was defined > 30% of the population stained moderate to strong. Results: Responder analysis: Expressions of THBS1 gene of the 6 patients who had clinical benefits (2: partial response, 2: positive adenocarcinoma cells in peritoneal cytology became negative, 2: remarkable decrease of ascites) were more than 2 folds higher than those of no responders. THBS1 expression was confirmed in 5 (83.3%) using IHC staining, who had significantly higher survival rate compared with that of the negative. Role of THBS1 expression: 17 patients (28.8%) was THBS1 positive and had significantly better prognosis compared with negative patients (1year survival: 64.7% vs 34.7%). 38 patients treated with regimes including taxanes revealed a tendency of improved overall survival rates (p=0.05). Overall survival of 15 patients with THBS1 positive administered taxanes was significantly higher than that of the negative patients. (1 year survival: 66.7% vs 42.4%) Conclusions: PTX could improve the survival of peritoneal metastasis of gastric cancer. THBS1 is a prognostic factor especially in the patients treated with taxanes, which leads to tailor-made therapy. [Table: see text]

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 35-35
Author(s):  
Norihiko Sugisawa ◽  
Etsuro Bando ◽  
Yuichiro Miki ◽  
Rie Makuuchi ◽  
Hironobu Goto ◽  
...  

35 Background: In type 4 gastric cancer, the incidence of peritoneal metastasis which was unexpectedly found during surgery was as high as 40 percent. It is very difficult to detect peritoneal metastasis in clinical imaging such as computed tomography or ultrasound before operation. Staging laparoscopy (SL) is considered to be an only minimal invasive procedure to detect peritoneal metastasis. However, the significance of SL had not yet been fully elucidated. The aim of this study is to assess the role of SL in type 4 gastric cancer. Methods: From September 2002 to March 2012, a total of 169 patients with type 4 gastric cancer who were diagnosed as not having distant metastasis in clinical imaging were enrolled in this study. SL was performed for 56 patients, and the other 113 patients underwent open laparotomy (OL) without SL. We retrospectively examined the incidence of peritoneal metastasis and positive peritoneal cytology and treatment courses in patients who underwent SL and OL. Results: In 56 patients undergoing SL, 23 (41%) had peritoneal metastasis and 40 (71%) had positive peritoneal cytology. Similarly, 54 (48%) had peritoneal metastasis and 86 (76%) had positive peritoneal cytology in 113 patients undergoing OL. There were no significant differences of the incidence of peritoneal metastasis and positive peritoneal cytology between the two groups. Subsequent treatments after SL or OL were diverse depends on patients condition and participating clinical trials, however, 17 (32%) in SL group and 13 (12%) in OL group were treated without surgical interventions. There was no morbidity and mortality in both SL group and OL group. In SL group, open surgery was performed soon afterword in 39 patients. Among them, 2 patients was failed to detect peritoneal metastasis by SL. Therefore the accuracy of detecting peritoneal metastasis in SL was 23/25 (92%). Conclusions: In type 4 gastric cancer, the incidence of peritoneal metastasis was around 40% and positive peritoneal lavage cytology was around 70% in both SL and OL. As SL is less invasive than OL, SL appears to be a useful way to detect peritoneal seeding and establish treatment strategy in patients with type 4 gastric cancer.


2014 ◽  
Vol 99 (6) ◽  
pp. 830-834 ◽  
Author(s):  
Okihide Suzuki ◽  
Minoru Fukuchi ◽  
Erito Mochiki ◽  
Toru Ishiguro ◽  
Jun Sobajima ◽  
...  

Abstract This retrospective study identified the optimal treatment strategy for patients with gastric cancer with positive peritoneal cytology. We analyzed clinicopathologic and survival data for 54 patients who had undergone gastrectomy and/or chemotherapy for treatment of gastric cancer with positive peritoneal cytology with (n = 40) or without (n = 14) metastatic disease. The median overall survival did not differ significantly between patients with gastric cancer with positive peritoneal cytology with and without metastatic disease (19 versus 13 months, respectively). Among 14 clinicopathologic variables, the lack of gastrectomy was the only significant independent unfavorable factor for survival (odds ratio, 1.64; 95% confidence interval, 1.04–2.57; P = 0.03). The median overall survival significantly differed among patients who had undergone gastrectomy plus chemotherapy, chemotherapy alone, and gastrectomy alone (25, 10, and 17 months, respectively; P < 0.01). Gastrectomy may be optimal for patients with (gastric cancer with positive peritoneal cytology), considering its favorable prognostic effect with respect to perioperative chemotherapy.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Massimiliano Valletti ◽  
Dilmurodjon Eshmuminov ◽  
Nicola Gnecco ◽  
Christian Alexander Gutschow ◽  
Paul Magnus Schneider ◽  
...  

Abstract Background The optimal treatment in patients with gastric cancer and peritoneal disease remains controversial. Some guidelines indicate palliative treatment only, while others consider surgical treatment in case of positive lavage cytology (CY+) or limited peritoneal disease. Here, we analyzed the role of peritoneal disease in patients with gastric cancer, and the prognostic relevance of response to neoadjuvant therapy. Methods In this retrospective cohort analysis, we analyzed patients with adenocarcinoma of the stomach or esophago-gastric junction from a single center operated between 2011 and 2019. According to histology and lavage cytology, patients were classified into four risk groups: (A) no peritoneal disease, (B) CY+ who converted to negative lavage cytology (CY−) after neoadjuvant chemotherapy, (C) CY+ without conversion after chemotherapy, and (D) patients with visible peritoneal metastasis. Results Overall, n = 172 patients were included. At initial presentation, n = 125 (73%) had no peritoneal disease, and about a third of patients (n = 47, 27%) had microscopic or macroscopic peritoneal disease. Among them, n = 14 (8%) were CY+ without visible peritoneal metastasis, n = 9 converted to CY− after chemotherapy, and in n = 5 no conversion was observed. Median overall survival was not reached in patients who had initially no peritoneal disease and in patients who converted after chemotherapy, resulting in 3-year survival rates of 65% and 53%. In contrast, median overall survival was reduced to 13 months (95% CI 8.7–16.7) in patients without conversion and was 16 months (95% CI 12–20.5) in patients with peritoneal metastasis without difference between the two groups (p = .364). The conversion rate from CY+ to CY− was significantly higher after neoadjuvant treatment with FLOT (5-fluorouracil plus leucovorin, oxaliplatin, and docetaxel) compared to ECF (epirubicin, cisplatin, and 5-fluorouracil) (p = 0.027). Conclusion Conversion of CY+ to CY− after neoadjuvant chemotherapy with FLOT is a significant prognostic factor for a better overall survival. Surgical treatment in well-selected patients should therefore be considered. However, peritoneal recurrence remains frequent despite conversion, urging for a better local control.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuyun Wu ◽  
Ningbo Hao ◽  
Suming Wang ◽  
Xin Yang ◽  
Yufeng Xiao ◽  
...  

Gastric cancer (GC) is one of the most common malignancies worldwide, and the tumor metastasis leads to poor outcomes of GC patients. Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules that play a crucial role in tumor metastasis. However, the biological function and underlying mechanism of numerous lncRNAs in GC metastasis remain largely unclear. Here, we report a novel lncRNA, lnc-TLN2-4:1, whose expression is decreased in GC tissue versus matched normal tissue, and its low expression is involved in the lymph node and distant metastases of GC, as well as poor overall survival rates of GC patients. We further found that lnc-TLN2-4:1 inhibits the ability of GC cells to migrate and invade but does not influence GC cell proliferation and confirmed that lnc-TLN2-4:1 is mainly located in the cytoplasm of GC cells. We then found that lnc-TLN2-4:1 increases the mRNA and protein expression of TLN2 in GC cells and there is a positive correlation between the expression of lnc-TLN2-4:1 and TLN2 mRNA in GC tissue. Collectively, we identified a novel lncRNA, lnc-TLN2-4:1, in GC, where lnc-TLN2-4:1 represses cell migration and invasion. The low expression of lnc-TLN2-4:1 is associated with poor overall survival rates of GC patients. These suggest that lnc-TLN2-4:1 may be a tumor suppressor during GC metastasis.


2012 ◽  
Vol 674 (2-3) ◽  
pp. 143-152 ◽  
Author(s):  
Luigina Graziosi ◽  
Andrea Mencarelli ◽  
Chiara Santorelli ◽  
Barbara Renga ◽  
Sabrina Cipriani ◽  
...  

2021 ◽  
Vol 27 ◽  
Author(s):  
Qi Zhang ◽  
Yinxin Wu ◽  
Jinlan Chen ◽  
Yuxuan Cai ◽  
Bei Wang ◽  
...  

Background: MBNL1, a protein encoded by q25 gene on chromosome 3, belongs to the tissue-specific RNA metabolic regulation family, which controls RNA splicing.[1]MBNL1 formed in the process of development drive large transcriptomic changes in cell differentiation,[2] it serves as a kind of tumor differentiation inhibitory factor.MBNL1 has a close relationship with cancer, comprehensive analysis, [3]found that breast cancer, leukemia, stomach cancer, esophageal adenocarcinoma, glial cell carcinoma and another common tumor in the cut, and cut in Huntington's disease. But MBNL1 plays a promoting role in cervical cancer, is contradictory in colorectal cancer, It promotes colorectal cancer cell proliferation, On the other hand, it inhibits its metastasis, so it is an important physiological marker in many cancers. When we integrated the role of MBNL1 protein in various tumors, we found that its antisense RNA, MBNL1-AS1, had a good inhibitory effect in several colorectal cancer, non-small cell lung cancer, and gastric cancer. Objective: To elucidate the expression of MBNL1 and MBNL1-AS1 in various tumors, and to search for their physiological markers. Methods: It was searched by the PUMUB system and summarized its expression in various cancers. Results: MBNL1 was down-regulated, leukemia, breast cancer, glioblastoma, gastric cancer, overall survival rate, recurrence, metastasis increased. While the metastasis of colon cancer decreased, proliferation was promoted, and the effect of both was promoted for cervical cancer.MBNL1-AS1 was down-regulated, and the overall survival rate, recurrence, and metastasis of lung cancer, colorectal cancer, and bladder cancer increased. Conclusion: MBNL1 may be an important regulator of cancer, and MBNL1-AS1 is a better tumor suppressor.


2019 ◽  
Vol 235 ◽  
pp. 607-614
Author(s):  
Natesh Yepuri ◽  
Nathan Bahary ◽  
Ajay Jain ◽  
Mashaal Dhir

2010 ◽  
Vol 8 (4) ◽  
pp. 417-425 ◽  
Author(s):  
Prajnan Das ◽  
Yixing Jiang ◽  
Jeffrey H. Lee ◽  
Manoop S. Bhutani ◽  
William A. Ross ◽  
...  

Most patients with localized gastric cancer require multimodality therapy. Surgery is the primary treatment for localized gastric cancer, although controversy exists about the optimal extent of lymphadenectomy in these patients. Recent studies have evaluated the role of laparoscopic surgery and endoscopic mucosal resection in selected patients. Multimodality treatment options for these patients include post-operative chemoradiation and perioperative chemotherapy. The Intergroup 0116 trial demonstrated that patients treated with surgery and post-operative chemoradiation had significantly higher overall survival compared to patients treated with surgery alone. The MAGIC trial showed that patients treated with perioperative epirubicin, cisplatin, and 5-fluorouracil had significantly higher overall survival compared to patients treated with surgery alone. Other recent trials have evaluated the roles of preoperative chemoradiation and adjuvant chemotherapy. Multidisciplinary evaluation plays a crucial role in the management of these patients.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10042-10042
Author(s):  
Juliette Thariat ◽  
Laurence Moureau-Zabotto ◽  
Nicolas Penel ◽  
Antoine Italiano ◽  
Jacques-Olivier Bay ◽  
...  

10042 Background: 40-50% of sarcomas become metastatic. Median survival of metastatic patients has improved over time. The probably multifactorial reasons for such improvement are not fully clear. Noteworthy, for patients with a controlled primary and a limited number of lung metastases, complete resection of their metastases yields survival rates of up to 40% at three years. Advances in surgery, radiotherapy and radiofrequency have fostered the use of local treatments for various metastatic sites (lung, liver, spine...). Methods: A multicentric retrospective study of the Groupe Sarcome Francais (GSF-GETO); approved by the nationally-review board and ethical committee, was conducted to assess the impact of local ablative treatment on overall survival. Patients who had had oligometastases (any site, 1-5 synchronous metastases) at diagnostic or during the course of disease between 2000 and 2010 were included. Results: Median age of the 243 oligometastatic sarcoma patients was 53 years-old (11-86). Patients had grade I, II and III in 7.5%, 29.6% and 63.3% of cases, respectively with various histologies. 69% of patients underwent local ablative treatment of metastases. Median follow-up was 59 months (4-212) for living patients. Median overall survival was 51 months (1-348). On univariate analysis, grade, histology, absence of chemotherapy, local ablative treatment (surgery, irradiation, radiofrequency or chemoembolisation) correlated with survival but not age or site of oligometastasis. On multivariate analyses, grade (hazard ratio HR 0.12 [CI95 0.3-0.6]) and local ablative treatment (HR 3.8 [CI95 2.1-7.1]) remained significant. Conclusions: Local ablative treatment of metastases is associated with better survival in sarcoma patients with oligometastatic disease. The role of the locoregional treatment of metastases and its impact on quality of life should be assessed prospectively.


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