[Two Cases of Advanced Recurrent Breast Cancer with Severe Heart Failure Caused By Anthracycline].

Case 1: A 48-year-old woman, had right breast cancer with multiple liver metastases. Seven courses of paclitaxel plus bevacizumab were administered, but due to disease progression, 12 courses of FEC 75(total epirubicin 900 mg/m2)were administered. 2 months after the last FEC administration, the patient developed heart failure and died about 3 months later. Case 2: A 58-year-old woman, was on endocrine therapy after surgery for left breast cancer. Recurrence of lung and bone metastases were appeared 5 years after surgery, 10 courses of FEC 75(total epirubicin 750 mg/m2)were administered due to disease progression. Eight months after the last administration of FEC, the patient developed heart failure and died about 8 months later. Anthracycline induced cardiotoxicity is irreversible and has a severe course. Therefore, anthracycline should be administered with caution.

[Two Cases of Advanced and Recurrent Gastric Cancer with Long-Term Survival Due to Successful Chemotherapy].

Case 1: A 73-year-old man underwent total gastrectomy for residual gastric cancer, and final pathological diagnosis was pStage ⅠB. Adjuvant chemotherapy was not performed. CT findings showed multiple liver metastasis 16 months after procedure. S-1 and CDDP were administered for 28 months. Although chemotherapy regimen was changed to S-1, paclitaxel plus ramucirumab, nivolumab, irinotecan and S-1 plus oxaliplatin(SOX)after progression, he died 73 months after operation, and 57 months after recurrence. Case 2: A 72-year-old man was pointed out swelling of gastric lymph nodes in CT imaging. He was diagnosed as advanced gastric cancer with para-aortic lymph node metastasis by followed examination. S- 1 plus CDDP was administrated for 30 months. S-1 and SOX were administered after progressive findings, but he died 48 months after diagnosis. We report 2 cases of recurrent and advanced gastric cancer with long-term survival because of successful chemotherapy.

SDF1α/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment.

Stromal cell-derived factor 1α (SDF1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4) have been reported to form an important chemokine signaling pathway. Our previous study reported that SDF1α from tumor stromal cells may stimulate the proliferation of gastric cancer (GC) cells through the CXCR4 axis in a hypoxic microenvironment. However, a limited number of studies have addressed the clinicopathological significance of the expression of SDF1α and CXCR4 in GC, particularly at hypoxic regions. Immunohistochemistry was used to investigate the expression levels of SDF1α, CXCR4 and the hypoxic marker carbonic anhydrase 9 (CA9) in 185 patients with stage II and III GC. The results demonstrated that CA9 was expressed on cancer and stromal cells in hypoxic lesions, CXCR4 was mainly expressed in cancer cells, and SDFα was mainly expressed in stromal cells. CXCR4 expression in cancer cells and SDFα expression in stromal cells were associated with the hypoxic regions with CA9 expression. The CA9 and CXCR4 expression in the cancer cells, and the SDF1α expression in the stromal cells (CA9/CXCR4/SDF1α) was significantly associated with macroscopic type 4 tumor (P=0.012) and the pattern of tumor infiltration into the surrounding tissue (P<0.001). The prognosis of the all CA9/CXCR4/SDF1α-positive patients was significantly poorer compared with that of patients with CA9-, CXCR4- or SDF1α-negative GC at Stage III (P=0.041). These results indicated that hypoxia may upregulate SDFα production in stromal cells and CXCR4 expression in cancer cells. The SDF1α/CXCR4 axis may serve an important role in the progression of GC.

[A Case of Metastatic Breast Cancer That Recovered from Diffuse Alveolar Damage Associated with Everolims].

A 68-year-old woman was receiving chemotherapy and endocrine therapy for right breast cancer postoperative pulmonary metastasis and local lymph node recurrence. However, she developed interstitial pneumonia 12 weeks after initiating treatment with everolimus and exemestane. Treatment with everolimus and exemestane was discontinued and steroid pulse therapy was initiated; however, she required ventilator management because of the severity of the pneumonia. The patient's condition improved 9 days after ventilator management. Everolimus-induced interstitial pneumonia is often mild, but it can be severe in rare cases. In our case, everolimus-induced diffuse alveoli damage was successfully treated with ventilator management.

[Three Cases of Unresectable Colorectal Cancer Curatively Resected after Effective Chemotherapy].

Case 1: A60-year-old man underwent resection of a brain tumor, which was pathologically diagnosed as adenocarcinoma. As he was diagnosed with unresectable rectal cancer due to pulmonary metastasis, we performed abdominoperineal resection after chemotherapy. Since pulmonary metastasis and local recurrence were detected 1 year after the surgery, he was administered chemotherapy. He died 37 months after the surgery. Case 2: A6 4-year-old man was diagnosed with unresectable rectal cancer due to pulmonary and hepatic metastases, resulting in an examination for melena. We performed laparoscopic low anterior resection and hepatic partial resection after chemotherapy. No relapse has occurred 1 year after the surgery. Case 3: A39 -year-old man was examined for abdominal pain and distension and was diagnosed with unresectable rectal cancer due to invasion of the left ureter and multiple hepatic metastases. We performed anterior resection, hepatic partial resection, and RFAafter chemotherapy. He has remained in relapse-free survival for 15 months after the surgery. These results suggest that curative resection after chemotherapy improves the prognosis of unresectable colorectal cancer.

[Analysis of Renal Toxicity of S-1 plus CDDP Regimen with Short Hydration for Outpatients with Gastric Cancer].

BACKGROUND: Although the S-1 plus CDDP(SP)regimen is the standard treatment for advanced gastric cancer, hydration and admission have been recommended after cisplatin has been administered. In this study, short hydration(SH)method was used and SP was administered in outpatient settings. We evaluated renal toxicity of cisplatin in the SH-SP regimen at our hospital. METHODS: Eleven of 16 patients(5 underwent only 1 course and so were excluded)received the SH-SP regimen between January 2012 and January 2018 to present and were included. Serum creatinine(Cr)and estimated glomerular filtration rate(eGFR)were used to assess renalfunction. RESULTS: Median course was 5. Rate of 5-course accomplishment was 72.7%. Grade 1 Cr elevation was observed in only 3 patients and there was no severe renal disorder. CONCLUSION: The SHSP regimen could be administered in outpatient settings and was considered safe as it did not cause renal toxicity.

[A Case of Breast Cancer Liver Metastases with Jaundice Responding to Chemotherapy].

A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.

Intraductal papillary mucinous neoplasm originating from a heterotopic pancreas within the jejunum: a case report.

We report a case of intraductal papillary mucinous neoplasm arising within the heterotopic pancreatic tissue which was found incidentally in the jejunum during surgery for bowel obstruction. A 54-year-old female patient was admitted to our hospital due to sudden abdominal pain. In preoperative findings, we diagnosed bowel obstruction and performed surgery. Intra-operative findings showed adhesive intestinal obstruction, we performed synechiotomy for adhesion release. During surgery, when searching the small intestine, we coincidentally found a tumor in the jejunum and partial resected the jejunum. Pathological examination revealed a 1.2 cm × 1.0 cm × 1.0 cm white yellow nodule with cystic spaces. Histological examination demonstrated heterotopic pancreatic tissue consisting of well-formed lobules of pancreatic acini and cystically dilated ducts containing intraductal papillary neoplasm. Moreover, in immunohistochemical staining, MUC5AC was diffusely expressed, but not MUC1, MUC2 and MUC6.

Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer.

BACKGROUND/AIMS: Lysyl oxidase (LOX) family members play a key role in modifying the primary tumor microenvironment by crosslinking collagens and elastin in the extracellular matrix. The aim of this study was to analyze the LOX-like (LOXL)1, LOXL3, and LOXL4 expressions in gastric cancer tissue by immunohistochemical staining. METHODS: The correlations between the clinicopathological features of 597 primary gastric carcinomas and LOX family members - LOXL1, LOXL3, and LOXL4 - were investigated by immunohistochemical studies. The effect of the transforming growth -factor ß1 (TGFß1) on the expressions of LOXL1, LOXL3, and LOXL4 in gastric cancer was examined using diffuse-type gastric cancer cell lines in vitro. RESULTS: The expressions of LOXL1, LOXL3, and LOXL4 were correlated with T invasion, lymph node metastasis, and lymphatic and venous invasion. LOXL1 expression was associated with histological intestinal-type and expanding growth patterns. The overall survival of patients with LOXL1-, LOXL3-, or LOXL4-positive cancer was poorer than those with negative cancer. LOXL3 and LOXL4 mRNA expressions were significantly high in diffuse-type gastric cancer cells with high invasion ability. TGFß decreased the LOXL1 expression and increased LOXL3 and LOXL4 expression. CONCLUSION: LOXL1, LOXL3, and LOXL4 expressions are associated with distant metastasis of gastric cancer.

Intracystic papillary carcinoma of the male breast: a case report.

BACKGROUND: Intracystic papillary carcinoma (IPC) is defined as cancer that develops from the wall of a cyst in the breast. As breast cancer in men accounts for only 1% of all breast cancers, male IPC is an extremely rare form of the disease. The present case report examines IPC in a man, along with an in-depth literature discussion. CASE PRESENTATION: A 64-year-old Japanese man noticed a mass in the right breast and sought medical attention. An elastic and soft neoplastic 3-cm lesion was palpated in the right papilla. As a 1-cm solid tumor with a gradual rise from the cyst wall was confirmed within the cyst, vacuum-assisted biopsy (VAB) was performed on that site. Pathological examination of the biopsy revealed heterotypic cells with an enlarged oval nucleus forming dense papillary structures mainly of vascular connective tissue component. Contrast-enhanced computed tomography (CT) confirmed thickening of the wall that protruded outside the cyst. The preoperative diagnosis was right breast cancer (male IPC) TisN0M0 stage 0 luminal B-like. Total mastectomy and sentinel lymph node biopsy were performed. In the excised specimen, a 4.0-cm unilocular cyst was found, along with a 1-cm solid tumor with a gradual rise from the cyst wall. Pathological diagnosis of the resected specimen shared similar characteristics with the solid tumor in the cyst: notably, an oval nucleus with histologically clear nucleolus and fine granular chromatin, cylindrically shaped heterotypic cells, and the presence of basophilic cells in the papillary growth with a thin stem of fibrovasculature as the axis. Some invasion of tumor cells into the interstitium was confirmed. As such, the final diagnosis was right breast cancer (male IPC) T2N0M0 stage IIA luminal B-like. The expression of hormone receptor (ER and PgR) was high, and endocrine therapy was initiated postoperatively (20 mg/day tamoxifen). At the present time (3 months postoperation), there has not been any evidence of metastasis. CONCLUSIONS: We reported a rare case of an IPC in the male breast, along with a literature review.

[Usefulness of Vacuum-Assisted Biopsy(VAB)at Initial Biopsy].

In recent years, breast micro-lesions such as ductal carcinoma in situ(DCIS)were detected with progress of the image diagnosis. We investigated the usefulness of vacuum-assisted biopsy(VAB)for initial biopsy of breast tumors. We analyzed 32 cases of VAB performed for breast tumors. The pathological diagnosis of the biopsy specimens was malignant lesions in 10 cases, border-line lesions in 1 and benign lesions in 21 cases. 11 cases underwent surgery and the final histopathological diagnosis was the same in 10 of them. One case histopathology varied from DCIS to invasive ductal carcinoma(IDC). It was suggested that VAB at initial biopsy was a useful biopsy method.

[A Case of Breast Cancer with Infarcted Necrosis That Was Diagnosed Based on Axillary Lymph Node Metastasis].

A 61-year-old woman with a breast tumor detected by mammography examination was admitted to our hospital. Ultrasonography showed a 15.5×7.2mm sized irregular mass at the left BD area. Vacuum-assisted biopsy did not reveal any malignant cells. After 3 months, ultrasonography reexamination showed that the irregular mass had increased to 24.2×16.5mm in size, and it had spread to multiple axillary lymph nodes. The patient was diagnosed with breast cancer by core needle biopsy of the axillary lymph node. Total mastectomy with axillary lymph node dissection was performed. The pathological diagnosis was solid-tubular carcinoma with infarcted necrosis. The number of metastatic axillary lymph nodes was confirmed to be 23 in total. This case was considered very rare and important because there have been very few reports of breast cancer with infarcted necrosis.

[A Case of Apocrine Carcinoma in the Breast That Was Difficult to Distinguish from Axillary Apocrine Adenocarcinoma].

An 86-year-old woman visited our hospital with a tumor on her right axilla. Ultrasonography(US)showed a 4 cm tumor between mammary gland and axilla with swelling of some lymph nodes. No distant metastatic lesions were found. The pathological findings revealed breast apocrine carcinoma; therefore, we performed total mastectomy and axillary lymph node dissection. The postoperative pathological findings revealed breast apocrine carcinoma with pT4N2M0, Stage Ⅲb(ER positive, PgR negative, HER2 positive, Ki-67 6%). We present a case of breast apocrine carcinoma confused with axially apocrine adenocarcinoma during the diagnosis and report the relevant literature.

Pyruvate kinase isozyme M2 and glutaminase might be promising molecular targets for the treatment of gastric cancer.

The aim of this study was to analyze the significance of glucose metabolism-related enzymes in the proliferation of gastric cancer under hypoxia. Four hypoxia-resistant gastric cancer cell lines and four parent cell lines were used. Reverse transcription-PCR was used to evaluate the mRNA expression levels of the following metabolism-related enzymes: pyruvate kinase isozyme M2 (PKM2), glutaminase (GLS), enolase 1 (ENO1), glucose-6-phosphate dehydrogenase (G6PDH), and PKM1. The effects of these enzymes on the proliferation of gastric cancer cells were examined using siRNAs, shikonin as a PKM2 inhibitor, or BPTES as a GLS inhibitor, in vitro and in vivo. Levels of both PKM2 and GLS mRNA were significantly high in all hypoxia-resistant cell lines, compared with those of their parent cells. Knockdown of PKM2 and GLS significantly decreased the proliferation of all hypoxia-resistant cells. The combination of siPKM2 and siGLS significantly decreased proliferation compared with treatment by siPKM2 or siGLS alone. The knockdown of ENO1, G6PDH, or PKM1 did not decrease the proliferation of all hypoxia-resistant cells. Combination treatment using shikonin and BPTES inhibited the proliferation of all hypoxia-resistant cancer cells more than that by either agent alone. The in vivo study indicated that the tumor size treated by the combination of shikonin and BPTES was significantly smaller than that of vehicle-treated group. These findings suggested that PKM2 and GLS might play important roles in the proliferation of hypoxic gastric cancer cells. A combination of PKM2 and GLS inhibitors could be therapeutically promising for the treatment of gastric cancer.

Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma.

PURPOSE: It was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer. METHODS: The correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies. The effect of gastric cancer cells on the expression of CXCR2 in BM-MCs was examined using diffuse-type gastric cancer cell lines in vitro. RESULTS: The expression of CXCL1 in cancer cells was correlated with T invasion (T2-T4), lymph node metastasis, lymphatic invasion, venous invasion, peritoneal cytology, peritoneal metastasis and CXCR2 expression in stromal cells. The expression of CXCR2 in stromal cells was correlated with macroscopic type-4 cancers, histological type, T invasion (T2-T4), lymph node metastasis, lymphatic invasion, infiltration, peritoneal cytology, peritoneal metastasis and CD271 expression in stromal cells. The overall survival of patients with CXCL1 and CXCR2-positive cancer was poorer than that of the patients with negative cancer. Both CXCL1 expression in cancer cells and CXCR2 expression in stromal cells were independent prognostic factors for gastric cancer patients. CONCLUSION: The expressions of CXCL1 in cancer cells and CXCR2 in stromal cells are useful prognostic factors for gastric cancer patients.

Kimura's disease affecting the axillary lymph nodes: a case report.

BACKGROUND: Kimura's disease (KD; eosinophilic granuloma of soft tissue) is an inflammatory granulomatous disorder of unknown cause with eosinophilic infiltration that occurs mainly in soft tissue. KD occurs mainly in the head and neck, but development in the axillary region is very rare. CASE PRESENTATION: A 74-year-old Japanese woman was evaluated for a mass that she noted in the left axillary region. On physical examination, there was a palpable, thumb-sized, hard, elastic, freely movable mass in the left axilla. Blood tests showed elevated soluble interleukin-2 receptor (sIL-2R), normal serum immunoglobulin (Ig) G4, and elevated serum IgE. Ultrasonography of the left axilla showed multiple lymph nodes (LNs) with irregular margins in which central hyperechogenicity was lost. A systemic search by computed tomography (CT) showed no systemic lymphadenopathy or other mass-like lesions suspicious for a primary tumour other than in the left axillary LNs. Biopsy of an excised LN was performed under local anaesthesia for a definitive diagnosis. Histopathology showed various-sized lymphoid follicles, large nodular lesions with an enlarged mantle zone, multiple various-sized germinal centres in single nodules, and eosinophilic infiltration between the nodes. Immunohistochemical (IHC) staining of the germinal centres was positive for cluster of differentiation (CD) 10, positive for B-cell lymphoma (bcl)-6, and negative for bcl-2. These findings led to a diagnosis of KD. Ultrasound after 3 months of follow-up showed disappearance of the axillary lymphadenopathy. CONCLUSIONS: A very rare case of KD in the axillary LNs was described. KD has the potential to occur in any region.

CXCL1-Chemokine (C-X-C Motif) Receptor 2 Signaling Stimulates the Recruitment of Bone Marrow-Derived Mesenchymal Cells into Diffuse-Type Gastric Cancer Stroma.

Tumor stromal cells play a critical role in the progression of diffuse-type gastric cancer (DGC). The aim of this study was to clarify where tumor stromal cells originate from and which factor(s) recruits them into the tumor stroma. Immunodeficient mice with bone marrow transplantation from the cytomegalovirus enhancer/chicken ß-actin promoter-enhanced green fluorescent protein mice were used for the in vivo experiments. An in vitro study analyzed the chemotaxis-stimulating factor from DGC cells using bone marrow-derived mesenchymal cells (BM-MCs). The influences of chemokine (C-X-C motif) receptor 2 (CXCR2) inhibitor on the migration of BM-MCs were examined both in vitro and in vivo. BM-MCs frequently migrated into stroma of DGC in vivo. The number of migrating BM-MCs was increased by conditioned medium from DGC cells. CXCL1 from DGC cells stimulated the chemoattractant ability of BM-MCs. Both anti-CXCL1 antibody and CXCR2 inhibitor decreased the migration of BM-MCs, stimulated by DGC cells. A CXCR2 inhibitor, SB225002, reduced the recruitment of BM-MCs into the tumor microenvironment in vivo, decreasing tumor size and lymph node metastasis, and prolonging the survival of gastric tumor-bearing mice. These findings suggested that most tumor stromal cells in DGC might originate from BM-MCs. CXCL1 from DGC cells stimulates the recruitment of BM-MCs into tumor stroma via CXCR2 signaling of BM-MCs. Inhibition of BM-MC recruitment via the CXCL1-CXCR2 axis appears a promising therapy for DGC.

Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs), the expression of insulin-like growth factor-1 (IGF1) and IGF1 receptor (IGF1R) was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9) was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2) and hypoxia (1% O2). IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.

Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer.

AIM: This study evaluated the clinicopathological significance of autophagy, an intracellular degradation system, in gastric cancer. MATERIALS AND METHODS: The expression levels of three autophagy-related proteins, namely light chain 3 (LC3), Beclin 1 and p62, were analyzed by immunohistochemistry using samples from 510 patients with primary gastric cancer. RESULTS: LC3, Beclin 1, and p62 expression was positive in 79 (15.5%), 126 (24.7%) and 251 (49.2%) out of 510 carcinomas, respectively. Autophagy was defined when samples were positive for at least two out of the three proteins. Autophagy-positive cases were 113 (22.1%) out of the 510. Autophagy determined by LC3, Beclin 1, and p62 significantly correlated with lymph node metastasis, vessel invasion, and hepatic metastasis. A Kaplan-Meier survival curve showed that autophagy was significantly associated with poor survival of patients with gastric cancer, especially for those with disease at stage I. Multivariate analysis indicated that autophagy was an independent prognostic factor. CONCLUSION: Autophagy promotes the progression of gastric cancer at an early clinical stage.

Lysyl oxidase is associated with the epithelial-mesenchymal transition of gastric cancer cells in hypoxia.

PURPOSE: It has been reported that lysyl oxidase (LOX) is a hypoxia-responsive factor and is associated with the malignant progression of carcinoma. The aim of this study was to clarify the relationship between the epithelial-mesenchymal transition (EMT) and LOX in gastric cancer cells under hypoxia. METHODS: Two gastric cancer cell lines, OCUM-2MD3 and OCUM-12, were used in an in vitro study. The effect of LOX small interfering RNA (siRNA) on the EMT and motility of gastric cancer cells under hypoxic condition was analyzed by reverse transcription PCR, Western blot, a wound-healing assay, and an invasion assay. Correlations between LOX expression and the clinicopathological features of 544 patients with gastric carcinoma were examined immunohistochemically. RESULTS: Hypoxic conditions increased the number of polygonal or spindle-shaped cells resulting from EMT in gastric cancer cells. The EMT of cancer cells induced by hypoxia was inhibited by treatment with LOX siRNA. The number of migrating and invading gastric cancer cells in hypoxia was significantly decreased by LOX knockdown. LOX siRNA significantly increased the E-cadherin level and decreased the vimentin level of gastric cancer cells. LOX expression was significantly associated with invasion depth, tumor differentiation, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal metastasis. Multivariable analysis revealed that LOX was an independent parameter for overall survival. CONCLUSION: LOX affects the EMT of gastric cancer cells in hypoxic conditions. LOX expression is a useful prognostic factor for patients with gastric cancer.