The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.
Most common metastatic tumors of the thyroid gland are squamous cell carcinoma of head and neck region, adenocarcinoma of breast and lung, malignant melanoma, and renal cell carcinoma of kidney in order of frequency. Metastasis from gastrointestinal tract to the thyroid gland rarely occurs. We experienced a case of fine needle aspiraton cytology of metastatic adenocarcinoma of both thyroid glands from the colon. Cytologic smears showed picket-fence like arrangement of nuclei of carcinoma cells and syncytial type of tissue fragments with acinar pattern on necrotic or mucoid background.
The increased use of cone-beam computed tomographic (CBCT) scans has made it increasingly necessary to evaluate incidental findings on CBCT scans. This report describes the case of a 66-year-old female patient who presented to the Department of Oral and Maxillofacial Pathology, Radiology and Medicine at the College of Dentistry of the author's institution and underwent a CBCT scan for maxillary alveolar process implant planning. Upon evaluation of the CBCT scan, a radiopaque (soft tissue attenuation) mass in the left superior aspect of the nasal cavity and left locule of the sphenoid sinus with opacification of the left locule of the sphenoid sinus was incidentally noted. These radiographic findings were suggestive of a space-occupying mass with a high possibility of malignancy. A further medical evaluation confirmed renal cell cancer metastasis to the sphenoid sinus. This study shows the significance of reviewing the entire CBCT scan for incidental findings.
Dirican, Ahmet;Kucukzeybek, Yuksel;Erten, Cigdem;Somali, Isil;Demir, Lutfiye;Can, Alper;Payzin, Kadriye Bahriye;Bayoglu, Ibrahim Vedat;Akyol, Murat;Yildiz, Yasar;Koseoglu, Mehmet;Alacacioglu, Ahmet;Tarhan, Mustafa Oktay
Asian Pacific Journal of Cancer Prevention
/
v.14
no.3
/
pp.2101-2105
/
2013
Background: Long-term survival is a problem with locally advanced and metastatic renal cell carcinomas. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, but data on sunitinib use as a second line treatment in metastatic renal cell carcinoma (mRCC) are limited. Prognostic and predictive value of peripheral blood markers has been shown for many cancers. Materials and Methods: Efficacy and safety profiles of sunitinib after interferon alpha (IFN-${\alpha}$) were evaluated based on retrospective data for 23 patients with mRCC. Hematological parameters (neutrophils, lymphocytes, platelets, mean platelet volume, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio) were recorded at the time of metastasis. It was evaluated whether hematological parameters were prognostic and predictive factors. Results: Median progression-free survival (PFS) time was 16.5 months (95%CI: 0-34.5). Median overall survival (OS) time was 25.7 months (95%CI: 10.8-40.0). Most common side effects were neutropenia (52.2%), stomatitis (26.1%) and hand-food syndrome (26.1%). PFS was found 3.13 vs 17.1 months in patients with neutrophil / lymphocyte ratio (NLR)>3 vs $NLR{\leq}3$ (p:0.012). Median OS was 6.96 vs 27.1 months in patients with NLR>3 vs $NLR{\leq}3$ (p:0.001).While 75% of patients who responded to sunitinib had $NLR{\leq}3$, in 72% of patients with no response to sunitinib NLR>3 was detected (p:0.036). The association between the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria and NLR was statistically significant (p:0.022). Conclusions: Data on second line sunitinib treatment following cytokine in mRCC are limited. In our study, we observed second line sunitinib treatment following IFN-${\alpha}$ to be effective and tolerable. NLRappeared to have prognostic and predictive value.
Park, Soo-Gon;Shin, Mi-Suk;Choi, Jin-Bong;Kim, Sun-Jong
Journal of Korean Medicine Rehabilitation
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v.19
no.1
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pp.91-102
/
2009
Objectives : The present study was carried out investigate the anti-cancer effect of Salvia miltiorrhiza, Carydalis turtschaminovii and Reynoutria elliptica herbal acupuncture on solid tumor of rats induced by injection of RK3E-ras cells. Methods : RK3E-ras cells were injected on the right lumbar region of rats. After 1 weeks, the experimental rats were divided into four groups : Control group, Salvia miltiorrhiza herbal acupuncture group(SM), Carydalis turtschaminovii herbal acupuncture group(CT), Reynoutria elliptica herbal acupuncture group(RE). And we investigated the weight and size of tumor tissue, gross anatomy, histological and PCNA immunohistochemical study, hepatic and renal metastasis for tumor of each group. Results : 1. In the weight of tumor tissue assessment, SM and CT's weight of tumor tissue was decreased. 2. In the size of tumor tissue assessment, SM was smaller than any other group. 3. In the histological observation, SM's formation of tunica fibrosa that surround the tumor cell was obvious and vasculature that developes circumference of tumor cell was not observed, and density of tumor cell was very low. 4. In the PCNA immunohistochemical study, Control group, SM, RE showed strong immune response in the central site of tumor tissue. 5. In observation of liver and kidney tissue, we were not able to observe tumor cell in the SM. Conclusions : Consequently, SM and CT showed a inhibition of growth and metastasis.
Kim, Jung-Hyun;Min, Daniel;Song, Sang-Hee;Lee, Ji-Hyun;Jeong, Hye-Cheol;Kim, Eun-Kyung
Tuberculosis and Respiratory Diseases
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v.74
no.4
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pp.169-176
/
2013
Background: Although the lung is a common site of metastasis, endobronchial metastases (EBM) from extrathoracic malignancies are rare. Previous studies were retrospective reviews of the cases from each single institute, and the last one was performed between 1992 and 2002. We evaluated the characteristics of patients with EBM who had been diagnosed in recent 10 years in our hospital. Methods: We retrospectively reviewed 1,275 patients who had undergone diagnostic bronchoscopic procedures between 2001 and 2011. An EBM was defined as bronchoscopically notable lesion, which was histopathologically identical to the primary tumor. Results: A total of 18 cases of EBM were identified. The mean age was 53 years, and 12 cases of the 18 patients were female. The most common primary malignancies were colorectal cancer and breast cancer (4 cases each), followed by cervix cancer (3 cases) and renal cell carcinoma (2 cases). Cough was the most common symptom. The most common radiologic finding was atelectasis, which was identified in 27.7% of the cases. The median interval from the diagnosis of primary malignancy to the diagnosis of EBM was 14 months (range, 0-112 months). The median survival time from the diagnosis of EBM was 10 months (range, 1-39 months). Conclusion: EBM from extrathoracic malignancies were rare. Colorectal cancer and breast cancer were common as primary malignancies. Fiberoptic bronchoscopy should be performed in all patients, who are suspected of having EBM. If atypical clinical and pathological features are present, appropriate diagnostic studies should be undertaken.
Upper tract urothelial carcinoma (UTUC) has a relatively low prevalence rate of about 1.8 per 100,000 people. According to the recent literature, the development of diagnostic techniques has gradually increased the prevalence and diagnosis rate. In the past, when UTUC was diagnosed, more than 60% of the patients were diagnosed as locally advanced or metastatic cancer. However, since 2010, approximately 70% of the patients have been diagnosed as operable stage. Although radical nephroureterectomy is known as the basis of treatment for UTUC, overall survival is poor in patients with lymph node invasion. Especially, the finding that a localized UTUC is associated with a high risk of cancer metastasis in approximately 50% of patients suggests that these patients may not have sufficient treatment through surgery alone. The European Association of Urology and the National Comprehensive Cancer Network guideline 2017 suggested that postoperative adjuvant chemotherapy may be considered in patients with advanced UTUC beyond pT2. Also, recent meta-analyses have reported that cisplatin-based adjuvant chemotherapy can be expected to have a synergistic effect of overall survival and disease-free survival. However, many patients with UTUC undergo postoperative renal failure, which may result in failure to perform cisplatin-based adjuvant chemotherapy with adequate dose. For this reason, several researchers have suggested that it is beneficial to apply neoadjuvant chemotherapy when the preoperative renal function is maintained to a certain extent. But, neoadjuvant chemotherapy has not been used by many clinicians because of the lack of studies and the rarity of the disease. We are currently discussing the outcomes and prospects of perioperative chemotherapy.
Journal of Physiology & Pathology in Korean Medicine
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v.26
no.2
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pp.228-233
/
2012
Two years ago, a 75-year-old female was diagnosed left renal cancer and went on radical nephrectomy. Recently, metastatized lesions on lumbar spine and various lymph nodes including paraaortic lymph node of which diameter was about 5.5 cm was identified. She suffered from extreme low back pain despite using opioid agents of fentanyl patch and oral oxycodone. During about one month, Korean medicine therpies including herbal medicine(Yang-He tang), acupuncture with her conventional medications were co-administered. However her pain didn't improved and gradual cough and dyspnea developed. So she transferred to the hemato-oncology part for 2 weeks under the diagnosis of everolimus-induced noninfectious pneumonitis. After quitting everolimus her pneumonitis was improved and she came back our ward and started another herbal medicine, Ai-Tong-Ning tang for about 2 months. During this period, her pain was well managed without oral opioid agents and her paraaortic lymph node was regressed to about 2.2cm in diameter.
Cho Eun-Chol;Sub Jin-Hak;Chung Woong-Yun;Kim Ho-Geun;Park Cheong-Soo
Korean Journal of Head & Neck Oncology
/
v.17
no.2
/
pp.205-209
/
2001
Purpose: Most cases of primary hyperparathyroidism are due to parathyroid adenoma or parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause of hyperparathyroidism. Although the diagnosis of parathyroid carcinoma is usually established by pathologic criteria especially of vascular or capsular invasion, some clinical and biochemical features differentiate it from benign forms of hyperparathyroidism. We under-took a retrospective study in 6 patients with parathyroid carcinoma, with the aim of conveying experience from management for this rare cause of hyperparathyroidism. Methods: Clinical symptoms, biochemical laboratory, radiologic, and intraoperative findings, local recurrence and distant metastasis were analyzed in 6 patients diagnosed pathologically as a parathyroid carcinoma after operation from 1992 to 2001. Results: Mean age was 50.2 years (33.0-60.0 years) and male to female ratio was 1:1. Neck mass was found in 5 patients, multiple bone pain in 3 patients and renal stone in 1 patient. One case has suffered from chronic renal failure for 19 years. Although preoperative laboratory evaluations showed the aspects of hyperparathyroidism in all cases, mean serum calcium level was 11.2mg/dl(10.5-12.1mg/dl), slightly elevated. Laboratory values after surgery were within the normal range in 5 cases. However, in one case with chronic renal failure, serum PTH levels, serially checked, were above the normal range. Any of imaging methods failed to suggest a parathyroid carcinoma preoperatively. Parathyroid adenoma was suspected in 3 cases, thyroid cancer in the other cases before surgery. The extent of resection was radical resection of parathyroid lesion with more than unilateral thyroid lobectomy and central compartment neck node dissection and in 2 cases, the resection of recurrent laryngeal nerve or strap muscles was added. During follow-up period, any local or systemic recurrence were not evident in all the cases. Conclusion: Although parathyroid carcinoma is a rare disease and its preoperative diagnosis, in our experience, could not easily be made, the understanding of characteristic clinical and biochemical feature could help diagnosis at first surgery. Radical resection without remaining residual tumor is most important for the management of the parathyroid cancer.
Hyperactivated ${\alpha}2$-6-sialylation on N-glycans due to overexpression of the Golgi enzyme ${\beta}$-galactoside: ${\alpha}2$-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This study was aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival of patients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391 patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at a single center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinical outcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016, respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 and p=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overall survival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002, respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expression remained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the UISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrence in ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk disease defined by the UISS score.
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