Ligand Bound Fatty Acid Binding Protein 7 (FABP7) Drives Melanoma Cell Proliferation Via Modulation of Wnt/β-Catenin Signaling

Pharmaceutical Research - Fatty acid-binding protein 7 (FABP7) involved in intracellular lipid dynamics, is highly expressed in melanomas and associated with decreased patient survival. Several...     

A retrospective study of parotid gland tumors at a single institution

The aim of the present study was to analyze the clinical characteristics, surgical treatments and clinical outcome of patients with parotid gland tumors and to compare the results with those cited in the literature. A retrospective study was conducted in 140 patients (male, n=77; female, n=63) with parotid gland tumors who underwent parotidectomy at Hokuto Hospital Department of Otolaryngology-Head and Neck Surgery (Obihiro, Japan) between April 2007 and December 2021. Of the 140 patients enrolled, 118 (84.3%) patients had benign tumors, including 63 (45%) patients with pleomorphic adenomas and 43 (30.7%) patients with Warthin tumors, and 22 patients (15.7%) had parotid carcinoma. Comparison of the three groups of patients with parotid gland tumors indicated that pack years as an indicator of smoking status were significantly higher in patients with Warthin tumors than in those with parotid carcinomas (P=0.011) or pleomorphic adenoma (P<0.001). Fine-needle aspiration cytology (FNAC) was non-diagnostic for only 6 (4.3%) of 140 patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC by both conventional smear and liquid-based cytology (LBC) for parotid carcinomas were 70, 99, 93.3, 94.4 and 82.9%, respectively. Among the 22 patients with parotid carcinoma, extended total/total and superficial parotidectomy were performed in 10 (45%) and 11 (50%) cases, respectively. Total and selective neck dissection of the area from level II to I, II and III were performed in 6 (24%) and 7 (32%) patients, respectively. Postoperative radiotherapy (50 Gy) was performed in 15 (68%) patients. The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 51.5 and 76.4%, respectively. Univariate analysis revealed that age >65 years was significantly associated with poorer 5-year OS (P<0.001) and DFS (P<0.001). Multivariate analysis revealed that an age of more than 65 years combined with high-grade histologic malignancy was associated with worse DFS (P=0.02; hazard ratio, 3.628; 95% confidence interval, 1.283-9.514). In conclusion, the clinical characteristics and treatment outcomes of parotid gland tumors were consistent with the results of previous reports. Smoking may be closely related to the pathogenesis of Warthin tumors. LBC potentially provides improved accuracy in FNAC.     

Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan

Background

Bone metastasis (BM) is important for studying systemic spread of breast cancer. It often causes skeletal-related events (SREs) that worsen quality of life. We investigated the prevalence and risk factors for BM and SRE using a dataset from the Breast Oncology Research Network (BORN) in Japan.

Patients and methods

We collected data on primary breast cancer patients with node-positive or node-negative disease at intermediate to high risk of recurrence. The risk factors affecting the BM-free rate, SRE-free rate and overall survival were analyzed by using the Cox proportional hazard model.

Results

Data of 1,779 patients who were diagnosed with breast cancer during 2003–2005 were collected from the BORN and 1,708 cases were used for analysis. The median follow-up duration was 5.71 years. BM developed in 193 cases (11.3 %) and the BM-free rate at 5 years was 89.2 %. The annual hazard ratio of BM development differs remarkably according to the tumor subtype. SREs occurred in 133 (68.9 %) out of 193 patients and the SRE-free rate at 5 years was 92.6 %. In the multivariate analysis, clinical stage (P < 0.0001), number of lymph node (LN) metastases (P = 0.0029), tumor subtype (P = 0.034) and progesterone receptor status (P = 0.038) were independently significant risk factors for BM-free rate, but only clinical stage (P < 0.0001) and number of LN metastases (P = 0.0004) significantly correlated with SRE-free rate.

Conclusions

This retrospective study clarifies the prevalence and risk factors for BM and SRE in Japanese breast cancer patients. Our results show the importance of considering subtype in the care of BM and SRE.     

Photodynamic therapy alone versus combined with intravitreal bevacizumab for neovascular age-related macular degeneration without polypoidal choroidal vasculopathy in Japanese patients

Background  

To compare 12-month results of two single initial treatments—photodynamic therapy with verteporfin alone (PDT group), and this therapy combined with intravitreal bevacizumab (IVB) (COMB group)—for neovascular age-related macular degeneration (AMD), not including patients with polypoidal choroidal vasculopathy (PCV) who were presumed to have AMD.     

Platinum and anthracycline therapy for advanced cutaneous squamous cell carcinoma

Background

Because metastatic cutaneous squamous cell carcinoma (CSCC) is rare, standard chemotherapy has not been fully established. In Japan, combination platinum and anthracycline chemotherapy has been used for elderly patients with advanced CSCC because of its low toxicity. However, the clinical benefit of this therapy has not been fully examined.

Methods

We retrospectively examined the response rate of combination platinum and anthracycline chemotherapy for metastatic CSCC.

Results

Eight patients received combination chemotherapy for metastatic lesions; there were lymph node lesions in 6 patients and skin and lung lesions in one patient each. The combination regimens were as follows: cisplatin (CDDP) (60–90 mg/m²/day, day 1) and adriamycin (ADM) (20–40 mg/m²/day, day 1 or 2) was administered in 5 patients; CDDP (10–15 mg/m²/day, days 1–5) and epirubicin (epi-ADM) (10–15 mg/m²/day, days 1–5) was administered in 2 patients; and carboplatin (CBDCA) (200–400 mg/m²/day, day 1) and ADM (20–40 mg/m²/day, day 1 or 2) was administered in one patient. The responses were as follows: complete response in 2 patients (CDDP + ADM for lung metastasis, CDDP + epi-ADM for lymph node metastasis), partial response in 1 (CDDP + ADM for lymph node metastasis), stable disease in 2, and progressive disease in 3. A durable response was observed in 2 patients showing complete responses (58 and 112 months).

Conclusions

The clinical effect of the combination of platinum and anthracycline for metastatic CSCC was limited despite the findings of two patients showing durable complete responses.     

Measurement and cellular sources of the soluble interleukin-2 receptor in primary central nervous system lymphoma

The aims of this study were to determine the diagnostic utility of the serum levels of the soluble interleukin 2 receptor (sIL-2R) as a tumor marker of primary central nervous system lymphoma (PCNSL) and to investigate the cellular source of sIL-2R using immunohistochemical staining. The serum sIL-2R levels of 37 samples from suspected PCNSL patients were measured. There were 13 patients with PCNSL and 24 patients with other diseases such as glioma, metastatic tumor, inflammation, or cerebrovascular disease. The serum sIL-2R levels of the PCNSL cases and other brain diseases were 629.5 ± 586.0 U/ml (mean ± SD; range 189–2220 U/ml) and 408.5 ± 250.7 U/ml (160–837 U/ml), respectively. The serum sIL-2R levels of the two groups overlapped, and hence the difference between them was not significant. sIL-2R is the α subunit of IL-2R. It is also known as CD25, and is cleaved from its position in the cell membrane and released into the blood. CD25 expression was immunohistochemically detected in 7 of 11 PCNSL samples. Confocal laser microscopy revealed that CD25 signals were present in atypical cells and mononuclear cells. We concluded that both lymphoma cells and infiltrating T cells express CD25, which is one of the cellular sources of sIL-2R.     

MicroRNA‐143/Musashi‐2/KRAS cascade contributes positively to carcinogenesis in human bladder cancer

It has been well established that microRNA (miR)‐143 is downregulated in human bladder cancer (BC). Recent precision medicine has shown that mutations in BC are frequently observed in FGFR3, RAS and PIK3CA genes, all of which correlate with RAS signaling networks. We have previously shown that miR‐143 suppresses cell growth by inhibiting RAS signaling networks in several cancers including BC. In the present study, we showed that synthetic miR‐143 negatively regulated the RNA‐binding protein Musashi‐2 (MSI2) in BC cell lines. MSI2 is an RNA‐binding protein that regulates the stability of certain mRNAs and their translation by binding to the target sequences of the mRNAs. Of note, the present study clarified that MSI2 positively regulated KRAS expression through directly binding to the target sequence of KRAS mRNA and promoting its translation, thus contributing to the maintenance of KRAS expression. Thus, miR‐143 silenced KRAS and MSI2, which further downregulated KRAS expression through perturbation of the MSI2/KRAS cascade.     

A case of multiple liver metastases of gastric cancer successfully treated by combination chemotherapy of S-1 and paclitaxel

A 54-year-old man underwent distal gastrectomy for early gastric cancer in September 2002. CT performed 6 months after the operation revealed liver metastases, and they were resected. Hepatic arterial infusion therapy of 5-FU was performed; however, multiple liver metastases appeared in October 2003. We added arterial infusion of CDDP to 5-FU, but liver metastases increased. We then applied a combination chemotherapy of S-1 and paclitaxel from February 2004. Subsequently, stable disease continued, and after 67 courses of S-1 plus paclitaxel, we changed the administration to S-1 alone from August 2009. After that, liver metastases did not increase, so we discontinued chemotherapy on August 2010, followed by observation. Progression of liver metastases has not been to date.