SignificanceTumors are composed of both cancer stem-like cells (CSCs) and differentiated cancer cells. Each CSC can undergo either a symmetric cell division to produce two CSCs or an asymmetric cell division to produce one CSC and one differentiated cancer cell. It is believed that the rate of symmetric division increases as more CSCs become malignant; however, underlying molecular mechanisms remain elusive. Here we show that stimulation with a cytokine, semaphorin (Sema), activates monooxygenase of MICAL3, a cytoplasmic signal transducer, through the neuropilin (NP) receptor that is specifically expressed on the breast CSC plasma membrane. The activation of MICAL3 induces symmetric division of CSCs. Each molecule in this signaling pathway represents a promising therapeutic target for eliminating CSCs.
It is unclear whether somatic copy number alterations (SCNAs) contribute to the development of colorectal cancer (CRC). Here, we aimed to identify the molecular profiles of early colorectal carcinogenesis based on SCNAs and determine the associations of other molecular abnormalities for the detection of neoplasia in both intramucosal neoplasia (IMN) and invasive CRC with invasion into the muscular layer without metastasis (early invasive CRC). A single nucleotide polymorphism array was used to examine 100 colorectal IMNs (low-grade adenoma [LGA], 40; high-grade adenoma [HGA], 25; intramucosal adenocarcinoma [IMA], 35) and early invasive CRC (20 tumors). In addition, genetic mutations (KRAS, BRAF), TP53 overexpression, microsatellite instability (MSI), and DNA methylation (low, intermediate, high) were examined. Hierarchical clustering analysis based on the SCNA pattern was carried out to identify molecular profiles in IMNs and early invasive CRC. Colorectal tumors were classified into three subgroups based on SCNA patterns. Subgroup 1 was characterized by multiple SCNAs, subgroup 3 was closely associated with infrequent SCNAs, and subgroup 2 was an intermediate subgroup in SCNA pattern between subgroups 1 and 3. Although mutations in KRAS were commonly found in all three subgroups, overexpression of TP53 was observed primarily in subgroup 1 and 2. DNA methylation showed a low/intermediate type. Finally, no MSI was detected. Each subgroup was correlated with histology (subgroup 1, early invasive CRC; subgroup 2, LGA; subgroups 2 and 3, HGA and IMA). Considerable SCNAs may be required for acquisition of invasive ability in CRC. Our results provide novel insights into early CRC.
We herein report two cases of locally advanced unresectable hepatocellular carcinoma (u‐HCC) that were resected after achieving a radiological complete response to initially administered lenvatinib followed by transcatheter arterial chemoembolization (LEN‐TACE sequential therapy). A 78‐year‐old woman and an 80‐year‐old man with HCC of Barcelona Clinic Liver Cancer classification stage C were treated for 15 and 14 months with lenvatinib, respectively. Both patients were subsequently treated with TACE, resulting in complete remission on imaging. The α‐fetoprotein level in the woman and man decreased markedly from 9370 ng/ml to 46 ng/ml and from 6380 ng/ml to 3 ng/ml, respectively, leading to hepatectomy. A histopathological examination showed coagulative necrosis of the entire HCC in one case, while the other showed a small population of viable HCC cells. The results showed that LEN‐TACE sequential therapy has a synergic effect and could be a promising option for locally advanced u‐HCC.
Background
This study aimed to evaluate the impact of previous local treatment on lymphatic drainage patterns in ipsilateral breast tumor recurrence (IBTR) based on our data on re-operative sentinel lymph node biopsy (re-SLNB) for IBTR.
Methods
Between April 2005 and December 2016, re-SLNB using lymphoscintigraphy with Tc-99 m phytate was performed in 136 patients with cN0 IBTR. Patients were categorized into two groups: the AX group included 55 patients with previous axillary lymph node dissection; the non-AX group included 69 patients with previous SLNB and 12 patients with no axillary surgery. The whole breast irradiation (RT) after initial surgery had performed in 17 patients in the AX group and 27 patients in the non-AX group.
Results
Lymphatic drainage was visualized in 80% of the AX group and 95% of the non-AX group (
P
< 0.01). The visualization rate of lymphatic drainage was associated with the number of removed lymph nodes in prior surgery. In the non-AX group, lymphatic drainage was visualized in 96% of patients without RT and 93% with RT. Lymphatic drainage was observed at the ipsilateral axilla in 98% of patients without RT and in 64% with RT (
P
< 0.0001). Aberrant drainage was significantly more common in patients with RT than without RT (60% vs. 19%,
P
< 0.001); it was observed mostly to the contralateral axilla (52% vs. 2%,
P
< 0.0001). In the AX group, patients with previous RT showed decreased lymphatic drainage to the ipsilateral axilla compared to those without RT (29% vs. 63%,
P
< 0.05) and increased aberrant drainage to the contralateral axilla (64% vs. 5%,
P
< 0.0001).
Conclusion
Lymphatic drainage patterns altered in re-SLNB in patients with IBTR and previous ALND and RT were associated with alterations in lymphatic drainage patterns.
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