Hisashi Onozawa

Upregulated Annexin A1 promotes cellular invasion in triple-negative breast cancer

Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein, involved in anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. While many studies have investigated the ANXA1 expression in various tumor types, the role of ANXA1 is not fully understood. Therefore, in the present study, we evaluated the ANXA1 expression in 211 breast cancer patients and compared the levels with clinicopathological factors. ANXA1 was positively expressed in 31 (14.7%) of the 211 cases in our cohort, and these positive cases were associated with triple-negative breast cancer (TNBC) (P=0.007) and venous invasion (P=0.028). The in vitro cell experiment found that the MDA-MB-231 cell line, which is a TNBC cell line, highly expressed ANXA1. Using this cell line, the functional role of ANXA1 in breast cancer was revealed and the knockdown of ANXA1 by specific siRNA demonstrated a significant reduction in cellular invasion. Further experiments indicated that ANXA1 was induced by hypoxia with hypoxia-inducible factor-1α induction. These results suggested that ANXA1, which enhanced breast cancer invasion and metastasis under hypoxia, were significantly associated with the worst patient outcome. This is particularly noted in TNBC, the group of breast cancer with the worst outcome for which new therapeutic implications are required.

Enhanced expression of KIF4A in colorectal cancer is associated with lymph node metastasis

Kinesin family member 4A (KIF4A) is a member of the kinesin 4 subfamily of kinesin-related proteins and serves an important role in cell division. The expression levels of KIF4A have been investigated in numerous types of cancer, including cervical, lung, oral, and breast cancer, and are established to be associated with poor patient prognosis. However, the role of KIF4A, as well as its expression in colorectal cancer (CRC), remains to be elucidated. Therefore, the current study investigated KIF4A expression levels in patients with CRC and demonstrated that its levels were increased in tumor tissues compared with non-tumor tissues. To investigate the functional role of KIF4A, KIF4A was knocked down in CRC cells and cell viability was evaluated. CRC cells with KIF4A knockdown exhibited lower cell proliferation compared with control cells. In addition, KIF4A expression levels, as determined by immunohistochemistry, were compared with the expression of Ki-67, but no significant associations were observed in the patients with CRC. Therefore, KIF4A was found to be upregulated in patients with CRC and downregulation of KIF4A reduced cell proliferation in CRC cells. These results suggest that KIF4A may be a potential therapeutic target, which may improve the outcomes of patients with CRC.

Multiple Metastatic Malignant Melanoma Presenting Intraluminal Gallbladder Bleeding

We report a case of malignant melanoma of unknown primary origin presenting metastasis in various organs as well as intraluminal gallbladder bleeding due to gallbladder metastasis. A 58-year-old woman was diagnosed with stage IV metastatic malignant melanoma. Because she exhibited acute cholecystitis and hemobilia due to malignant melanoma of the gallbladder, laparoscopic cholecystectomy was performed to relieve the symptoms. The resected gallbladder specimen showed a pedunculated black mass indicating malignant melanoma. Pathologic examination and immunohistochemical analysis revealed malignant melanoma of the gallbladder. Only a few cases of gallbladder malignant melanoma presenting hemobilia have been reported; here we present our case, including the experience of multidisciplinary treatment.

Upregulated solute carrier family 37 member 1 in colorectal cancer is associated with poor patient outcome and metastasis

Solute carrier (SLC) drug transporters exchange various molecules without energy from adenosine triphosphate hydrolysis, indicating an association with anticancer drug resistance. However, the expression and role of SLC transporters in malignant tumors has not yet been fully elucidated. Therefore, in the current study, the expression of SLC37A family genes was evaluated in patients with colorectal cancer (CRC), and it was revealed that SLC family 37 member 1 (SLC37A1) expression was significantly increased in tumorous tissues compared with that in non-tumorous tissues. The cases with upregulated expression of SLC37A1 by immunohistochemical staining were significantly associated with positive venous invasion and liver metastasis. Furthermore, upregulated SLC37A1 expression was associated with poor overall survival time in the present cohort. These results indicated that SLC37A1 is involved in the hematogenous metastasis of CRC. To investigate whether SLC37A1 is associated with hematogenous metastasis and glycolipid metabolism, SLC37A1 was knocked down in colon cancer cells, and the expression of sialyl Lewis A and sialyl Lewis X was observed to be decreased. In summary, upregulation of SLC37A1 was observed in patients with CRC, and was associated with poor patient outcomes and survival. To the best of our knowledge, the present study is the first to propose a key role of SLC37A1 in CRC, and additional studies are warranted to reveal the functional role of SLC37A1 in CRC development.

Upregulated HOXA9 expression is associated with lymph node metastasis in colorectal cancer

Homeobox A (HOXA) cluster genes, members of the HOX family, perform an important role in normal organ development. It has previously been reported that HOXA gene expression in various types of cancer is associated with poor patient outcomes. However, the role of HOXA genes, as well as their expression, in colorectal cancers (CRC) remains unknown. Therefore, the present study investigated HOXA gene expression in patients with CRC and revealed that HOXA9 expression was significantly increased in tumor tissues compared with non-tumor tissues. Additionally, the functional role of HOXA9 was assessed by knocking down the HOXA9 gene in CRC cells and by evaluating cell growth. Regarding gene expression, cases with positive HOXA9 expression (as detected by immunohistochemical staining) were significantly associated with higher TNM stage and positive lymph node metastasis, although no association was observed between increased HOXA9 levels and the rate of overall survival in the present cohort. Regarding the functional role, HOXA9 expression was demonstrated to be upregulated in patients with CRC and was associated with lymph node metastasis.

Do the types of perforation impact the outcomes in perforated stage II/III colorectal cancer patients?

Purpose: To compare the oncological outcomes between colorectal cancer (CRC) patients with tumor perforation and those with perforation proximal to the tumor. Patients and methods: Medical charts of 39 patients who underwent emergency surgery for colonic perforation related to potentially curable CRC were reviewed. Results: Eighteen patients developed tumor perforation (group A), whereas 21 patients developed perforation proximal to the tumor (group B). Twenty-four patients were pathological stage II and 15 patients were stage III. There were no significant differences in the clinicopathological and surgical data, including hospital mortality, between the groups; however, the incidence of diffuse peritonitis was higher in group B than that in group A (P < 0.01). The induction rates of adjuvant chemotherapy for survivors were identical between the two groups. Disease-free and overall survival periods did not significantly differ between the groups. Conclusion: Perforation type was not found to be associate...