Biomedicines

Research

Jump to: Review

14 pages, 1718 KiB

Open AccessArticle

Clinical Significance of Preoperative Hematological Parameters in Patients with D2-Resected, Node-Positive Stomach Cancer

by Jun Su Park, Jeong Il Yu, Do Hoon Lim, Heerim Nam, Young Il Kim, Jeeyun Lee, Won Ki Kang, Se Hoon Park, Seung Tae Kim, Jung Yong Hong, Tae Sung Sohn, Jun Ho Lee, Ji Yeong An, Min Gew Choi and Jae Moon Bae

Biomedicines 2022, 10(7), 1565; https://doi.org/10.3390/biomedicines10071565 - 30 Jun 2022

Cited by 2 | Viewed by 2049

Abstract

The purpose of the present study was to investigate the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer, and to explore who might benefit from adjuvant concurrent chemoradiotherapy (CCRT) compared to chemotherapy alone. Among 1032 patients with node-positive stomach [...] Read more.

The purpose of the present study was to investigate the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer, and to explore who might benefit from adjuvant concurrent chemoradiotherapy (CCRT) compared to chemotherapy alone. Among 1032 patients with node-positive stomach cancer who had a confirmed diagnosis after complete D2 resection, and who received adjuvant chemotherapy alone or CCRT, a total of 692 patients was selected using propensity score matching. Among absolute neutrophil count, absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, AMC was the most relevant prognostic factor for overall survival and recurrence-free survival (hazard ratio (HR) 1.674, 95% confidence interval (CI) 1.180–2.376; HR 1.908, 95% CI 1.650–2.695, respectively). In a subgroup with a high ALC, patients treated with adjuvant CCRT had a favorable recurrence-free survival (HR 0.620, 95% CI 0.393–0.980) compared to those treated with chemotherapy alone. Further study is needed to confirm our findings and to develop tailored adjuvant treatment. Full article

(This article belongs to the Special Issue Gastric Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

12 pages, 1517 KiB

Open AccessArticle

Palliative Radiotherapy for Bleeding from Unresectable Gastric Cancer Using Three-Dimensional Conformal Technique

by Hideaki Kawabata, Takashi Fujii, Tetsuya Yamamoto, Hiroaki Satake, Katsutoshi Yamaguchi, Yuji Okazaki, Kojiro Nakase, Masatoshi Miyata and Shigehiro Motoi

Biomedicines 2022, 10(6), 1394; https://doi.org/10.3390/biomedicines10061394 - 13 Jun 2022

Cited by 3 | Viewed by 2260

Abstract

Optimal regimens using recent radiotherapy (RT) equipment for bleeding gastric cancer (GC) have not been fully investigated yet. We retrospectively reviewed the clinical data of 20 patients who received RT for bleeding GC in our institution between 2016 and 2021. Three-dimensional conformal RT [...] Read more.

Optimal regimens using recent radiotherapy (RT) equipment for bleeding gastric cancer (GC) have not been fully investigated yet. We retrospectively reviewed the clinical data of 20 patients who received RT for bleeding GC in our institution between 2016 and 2021. Three-dimensional conformal RT was performed. The effectiveness of RT was evaluated by the mean serum hemoglobin (Hb) level and the number of transfused red blood cell (RBC) units 1 month before and after RT. The median first radiation dose was a BED of 39.9 Gy. The treatment success rate was 95% and the rebleeding rate was 10.5%. There was a significant increase in the mean Hb level (8.0 ± 1.1 vs. 9.8 ± 1.3 g/dL, p = 0.01), and a significant decrease in the mean number of transfused RBC units (6.8 ± 3.3 vs. 0.6 ± 1.5 units, p < 0.01). Severe toxicity was observed in two patients (anorexia [n = 1] and gastrointestinal [GI] perforation [n = 1]). Reirradiation was attempted in three patients (for hemostasis [n = 2] and for mass reduction [n = 1]). The retreatment success rate for rebleeding was 100%. GI perforation occurred in two patients who had received hemostatic reirradiation. Palliative RT for bleeding GC using recent technology had excellent efficacy. However, it may be associated with a risk of GI perforation. Full article

(This article belongs to the Special Issue Gastric Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

11 pages, 1042 KiB

Open AccessArticle

Calculated Tumor-Associated Neutrophils Are Associated with the Tumor—Stroma Ratio and Predict a Poor Prognosis in Advanced Gastric Cancer

by Eun Young Kim, Jamshid Abdul-Ghafar, Yosep Chong and Kwangil Yim

Biomedicines 2022, 10(3), 708; https://doi.org/10.3390/biomedicines10030708 - 18 Mar 2022

Cited by 14 | Viewed by 2814

Abstract

The tumor-associated neutrophils (TANs) value and tumor—stroma ratio (TSR) are promising prognostic parameters in the tumor microenvironment. We aimed to evaluate the prognostic role and relationship of TANs and TSR in gastric cancer. Our study comprised 157 patients who underwent gastrectomy for advanced [...] Read more.

The tumor-associated neutrophils (TANs) value and tumor—stroma ratio (TSR) are promising prognostic parameters in the tumor microenvironment. We aimed to evaluate the prognostic role and relationship of TANs and TSR in gastric cancer. Our study comprised 157 patients who underwent gastrectomy for advanced gastric cancer. TANs were assessed by immunohistochemical staining (CD15 and CD66b) and were analyzed with an image analyzer. TANs have been known to have different functional subpopulations of N1 (anti-tumor) and N2 (pro-tumor). We developed “calculated TANs with pro-tumor function (cN2; CD15 minus CD66b)”. The TSR was evaluated using hematoxylin and eosin staining. High-grade CD15-positive, cN2 in the tumor center, and TSR were significantly related to poor disease-free survival (DFS). TSR and cN2 were independent prognostic factors for DFS (hazard ratio (HR) = 2.614; p = 0.001, HR = 3.976; p = 0.002) and cN2 in the tumor center showed a positive correlation with TSR (R = 0.179, p = 0.025). While CD66b stained both N1 and N2, CD15 detected most of N2. Combining both markers revealed a novel cN2, which was an independent marker of poor prognosis. The transformation from N1 to N2 predominantly occurred in the tumor center, and was associated with TSR. Full article

(This article belongs to the Special Issue Gastric Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

18 pages, 10329 KiB

Open AccessArticle

E-Cadherin Modulation and Inter-Cellular Trafficking in Tubular Gastric Adenocarcinoma: A High-Resolution Microscopy Pilot Study

by Ilona Mihaela Liliac, Bogdan Silviu Ungureanu, Claudiu Mărgăritescu, Victor Mihai Sacerdoțianu, Adrian Săftoiu, Laurențiu Mogoantă, Emil Moraru and Daniel Pirici

Biomedicines 2022, 10(2), 349; https://doi.org/10.3390/biomedicines10020349 - 1 Feb 2022

Cited by 2 | Viewed by 2508

Abstract

Despite the numerous advances in tumor molecular biology and chemotherapy options, gastric adenocarcinoma is still the most frequent form of gastric cancer. One of the core proteins that regulates inter-cellular adhesion, E-cadherin plays important roles in tumorigenesis as well as in tumor progression; [...] Read more.

Despite the numerous advances in tumor molecular biology and chemotherapy options, gastric adenocarcinoma is still the most frequent form of gastric cancer. One of the core proteins that regulates inter-cellular adhesion, E-cadherin plays important roles in tumorigenesis as well as in tumor progression; however, the exact expression changes and modulation that occur in gastric cancer are not yet fully understood. In an attempt to estimate if the synthesis/degradation balance matches the final membrane expression of this adhesion molecule in cancer tissue, we assessed the proportion of E-cadherin that is found in the Golgi vesicles as well as in the lysosomal pathway We utilized archived tissue fragments from 18 patients with well and poorly differentiated intestinal types of gastric cancer and 5 samples of normal gastric mucosa, by using high-magnification multispectral microscopy and high-resolution fluorescence deconvolution microscopy. Our data showed that E-cadherin is not only expressed in the membrane, but also in the cytoplasm of normal and tumor gastric epithelia. E-cadherin colocalization with the Golgian vesicles seemed to be increasing with less differentiated tumors, while co-localization with the lysosomal system decreased in tumor tissue; however, the membrane expression of the adhesion molecule clearly dropped from well to poorly differentiated tumors. Thus E-cadherin seems to be more abundantly synthetized than eliminated via lysosomes/exosomes in less differentiated tumors, suggesting that post-translational modifications, such as cleavage, conformational inactivation, or exocytosis, are responsible for the net drop of E-cadherin at the level of the membrane in more anaplastic tumors. This behavior is in perfect accordance with the concept of partial epithelial-to-mesenchymal transition (P-EMT), when the E-cadherin expression of tumor cells is in fact not downregulated but redistributed away from the membrane in recycling vesicles. Moreover, our high-resolution deconvolution microscopy study showed for the first time, at the tissue level, the presence of Lysosome-associated membrane glycoprotein 1 (LAMP1)-positive exosomes/multivesicular bodies being trafficked across the membranes of tumor epithelial cells. Altogether, a myriad of putative modulatory pathways is available as a treatment turning point, even if we are to only consider the metabolism of membrane E-cadherin regulation. Future super-resolution microscopy studies are needed to clarify the extent of lysosome/exosome exchange between tumor cells and with the surrounding stroma, in histopathology samples or even in vivo. Full article

(This article belongs to the Special Issue Gastric Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

Review

Jump to: Research

12 pages, 291 KiB

Open AccessReview

Treatment Response Predictors of Neoadjuvant Therapy for Locally Advanced Gastric Cancer: Current Status and Future Perspectives

by Yasushi Sato, Koichi Okamoto, Tomoyuki Kawaguchi, Fumika Nakamura, Hiroshi Miyamoto and Tetsuji Takayama

Biomedicines 2022, 10(7), 1614; https://doi.org/10.3390/biomedicines10071614 - 6 Jul 2022

Cited by 6 | Viewed by 2538

Abstract

Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, [...] Read more.

Neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) has been recognized as an effective therapeutic option because it is expected to improve the curative resection rate by reducing the tumor size and preventing recurrence of micrometastases. However, for patients resistant to NAC, not only will operation timing be delayed, but they will also suffer from side effects. Thus, it is crucial to develop a comprehensive strategy and select patients sensitive to NAC. However, the therapeutic effect of NAC is unpredictable due to tumor heterogeneity and a lack of predictive biomarkers for guiding the choice of optimal preoperative treatment in clinical practice. This article summarizes the related research progress on predictive biomarkers of NAC for gastric cancer. Among the many investigated biomarkers, metabolic enzymes for cytotoxic agents, nucleotide excision repair, and microsatellite instability, have shown promising results and should be assessed in prospective clinical trials. Noninvasive liquid biopsy detection, including miRNA and exosome detection, is also a promising strategy. Full article

(This article belongs to the Special Issue Gastric Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Graphical abstract

17 pages, 1249 KiB

Open AccessReview

Molecular Mechanisms and Potential Rationale of Immunotherapy in Peritoneal Metastasis of Advanced Gastric Cancer

by Donghoon Kang and In-Ho Kim

Biomedicines 2022, 10(6), 1376; https://doi.org/10.3390/biomedicines10061376 - 10 Jun 2022

Cited by 10 | Viewed by 3544

Abstract

Peritoneal metastasis (PM) is one of the most frequent metastasis patterns of gastric cancer (GC), and the prognosis of patients with PM is very dismal. According to Paget’s theory, disseminated free cancer cells are seeded and survive in the abdominal cavity, adhere to [...] Read more.

Peritoneal metastasis (PM) is one of the most frequent metastasis patterns of gastric cancer (GC), and the prognosis of patients with PM is very dismal. According to Paget’s theory, disseminated free cancer cells are seeded and survive in the abdominal cavity, adhere to the peritoneum, invade the subperitoneal tissue, and proliferate through angiogenesis. In these sequential processes, several key molecules are involved. From a therapeutic point of view, immunotherapy with chemotherapy combination has become the standard of care for advanced GC. Several clinical trials of newer immunotherapy agents are ongoing. Understanding of the molecular process of PM and the potential rationale of immunotherapy for PM treatment is necessary. Beyond understanding of the molecular aspect of PM, many studies have been conducted on the modality of treatment of PM. Notably, intraperitoneal approaches, including chemotherapy or immunotherapy, have been conducted, because systemic treatment of PM has limitations. In this study, we reviewed the molecular mechanisms and immunologic aspects of PM, and intraperitoneal approaches under investigation for treating PM. Full article

(This article belongs to the Special Issue Gastric Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

18 pages, 6995 KiB

Open AccessReview

Gastric Cancer: Mechanisms, Biomarkers, and Therapeutic Approaches

by Sangjoon Choi, Sujin Park, Hyunjin Kim, So Young Kang, Soomin Ahn and Kyoung-Mee Kim

Biomedicines 2022, 10(3), 543; https://doi.org/10.3390/biomedicines10030543 - 24 Feb 2022

Cited by 20 | Viewed by 4453

Abstract

Gastric cancer (GC) remains one of the most common deadly malignancies worldwide. Recently, several targeted therapeutics for treating unresectable or metastatic GC have been developed. Comprehensive characterization of the molecular profile and of the tumor immune microenvironment of GC has allowed researchers to [...] Read more.

Gastric cancer (GC) remains one of the most common deadly malignancies worldwide. Recently, several targeted therapeutics for treating unresectable or metastatic GC have been developed. Comprehensive characterization of the molecular profile and of the tumor immune microenvironment of GC has allowed researchers to explore promising biomarkers for GC treatment and has enabled a new paradigm in precision-targeted immunotherapy. In this article, we review established and promising new biomarkers relevant in GC, with a focus on their clinical implications, diagnostic methods, and the efficacy of targeted agents. Full article

(This article belongs to the Special Issue Gastric Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

23 pages, 793 KiB

Open AccessEditor’s ChoiceReview

Biomarkers for Gastric Cancer Screening and Early Diagnosis

by Cristina Herrera-Pariente, Sheyla Montori, Joan Llach, Alex Bofill, Eduardo Albeniz and Leticia Moreira

Biomedicines 2021, 9(10), 1448; https://doi.org/10.3390/biomedicines9101448 - 12 Oct 2021

Cited by 32 | Viewed by 4976

Abstract

Gastric cancer is one of the most common cancers worldwide, with a bad prognosis associated with late-stage diagnosis, significantly decreasing the overall survival. This highlights the importance of early detection to improve the clinical course of these patients. Although screening programs, based on [...] Read more.

Gastric cancer is one of the most common cancers worldwide, with a bad prognosis associated with late-stage diagnosis, significantly decreasing the overall survival. This highlights the importance of early detection to improve the clinical course of these patients. Although screening programs, based on endoscopic or radiologic approaches, have been useful in countries with high incidence, they are not cost-effective in low-incidence populations as a massive screening strategy. Additionally, current biomarkers used in daily routine are not specific and sensitive enough, and most of them are obtained invasively. Thus, it is imperative to discover new noninvasive biomarkers able to diagnose early-stage gastric cancer. In this context, liquid biopsy is a promising strategy. In this review, we briefly discuss some of the potential biomarkers for gastric cancer screening and diagnosis identified in blood, saliva, urine, stool, and gastric juice. Full article

(This article belongs to the Special Issue Gastric Cancer: From Mechanisms to Therapeutic Approaches)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Gastric Cancer: From Mechanisms to Therapeutic Approaches

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI