The effect of perovskite film thickness on the current density (
J
)-voltage (
V
) hysteresis is investigated with a normal planar perovskite solar cell (PSC) having the FTO/ETL/MAPbI
3
.../spiro-MeOTAD/Au structure (ETL = electron transporting layer, MA = methylammonium, and spiro-MeOTAD = 2,2′,7,7′-tetrakis-(
N
,
N
-di-4-methoxyphenylamino)-9,9′-spirobifluorene). A compact TiO
2
(c-TiO
2
) layer is used as an ETL, which is compared with a PCBM ETL and a c-TiO
2
/PCBM bilayered ETL. The MAPbI
3
layer thickness is varied from 100 nm to 800 nm by controlling the precursor solution concentration. The hysteresis increases with perovskite layer thickness for the c-TiO
2
layer, while the hysteresis decreases with increasing the perovskite layer thickness in the presence of PCBM. Deep trap states are much more reduced upon inserting PCBM compared with those of the c-TiO
2
case, indicative of fewer traps for non-radiative recombination. The ideality factor obtained from the light-dependent open-circuit voltage (
V
oc
) increases for the c-TiO
2
layer but decreases for both the c-TiO
2
/PCBM bilayer and the PCBM layer as the perovskite layer thickness increases, which again supports that the dependence of hysteresis on the perovskite thickness is related to trap states, that is, decreases in deep trap states can reduce hysteresis. From the capacitance-frequency studies, it is found that the low-frequency capacitance correlates with the observed hysteresis, where it increases for the c-TiO
2
layer but decreases for the PCBM containing ETLs with perovskite thickness. This work provides important insight into the hysteresis behavior of PSCs, where the hysteresis depends not only on the nature of the ETL but also on the degree of recombination in the bulk perovskite.
The effect of perovskite film thickness on the current density (
J
)-voltage (
V
) hysteresis is investigated with a normal planar perovskite solar cell (PSC) having the FTO/ETL/MAPbI
3
/spiro-MeOTAD/Au structure (ETL = electron transporting layer, MA = methylammonium, and spiro-MeOTAD = 2,2′,7,7′-tetrakis-(
N
,
N
-di-4-methoxyphenylamino)-9,9′-spirobifluorene).
Background
Lateral pelvic lymph node dissection (LPND) is a technically demanding procedure. Consequently, there is a possibility of incomplete dissection of lateral pelvic lymph nodes (LPNs). We ...aimed to identify metastatic LPNs intraoperatively in real-time under dual guidance of fluorescence imaging and 3D lymphovascular reconstruction, and then to remove them completely.
Methods
Rectal cancer patients who were scheduled to undergo LPND after preoperative chemoradiotherapy (CRT) were prospectively enrolled. We traced changes in suspected metastatic LPNs during preoperative CRT and defined them as
index
LPNs on post-CRT imaging studies. For fluorescence imaging, indocyanine green (ICG) at a dose of 2.5 mg was injected transanally around the tumor before the operation. For 3D reconstruction images, each patient underwent preoperative axial CT scan with contrast (0.6 mm slice thickness). These images were then manipulated with OsiriX.
Index
LPNs and essential structures in the pelvic sidewall, such as the obturator nerve, were reconstructed with abdominal arteries from 3D volume rendering. All surgical procedures were performed via laparoscopic or robotic approach.
Results
From March to July 2017, ten rectal cancer patients underwent total mesorectal excision with LPND after preoperative CRT under dual image guidance. Bilateral LPND was performed in five patients. All
index
LPNs among ICG-bearing lymph nodes were clearly identified intraoperatively by matching with their corresponding 3D images. Pathologic LPN metastasis was confirmed in four patients (40.0%) and in five of the 15 dissected pelvic sidewalls (33.0%). All metastatic LPNs were identified among
index
LPNs. Four (80.0%) of the five metastatic LPNs were located in the internal iliac area.
Conclusion
Index
LPNs among ICG-bearing lymph nodes in pelvic sidewall were clearly identified and completely removed by matching with their corresponding 3D reconstruction images. Further studies and long-term oncologic outcomes are required to determine the real impact of dual image guidance in LPND.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Photothermal therapy (PTT) has garnered considerable attention as an attractive treatment tool for cancer due to precisely selective treatment and minimal side effects. The primary challenge of PTT, ...which hinders its widespread application, is the limited therapeutic depth. This limitation arises from optical scattering in biological tissues, causing inadequate heat distribution within the deep tissue. To overcome this challenge, ultrasound‐assisted PTT (ULTRA‐PTT) is proposed that leverages the temporary formation of gas bubbles induced by ultrasound within the light propagation path. These bubbles act as optical clearing agents, effectively reducing optical scattering in biological tissues. To facilitate ULTRA‐PTT, a dedicated handpiece consisting of a ring‐shaped ultrasound transducer and a laser delivery module is developed. In‐vivo experiments show that ULTRA‐PTT statistically outperforms conventional PTT in melanoma treatment, mostly due to its ability to deliver sufficient laser energy to deep‐seated cancer cells. These findings underscore the potential of ULTRA‐PTT to expand the clinical applications of PTT beyond local tumors occurring in superficial tissue.
Photothermal therapy (PTT) is a promising cancer treatment due to its precise targeting and minimal side effects. However, its limited therapeutic depth poses a challenge due to optical scattering in tissues. To address this, ultrasound‐assisted PTT (ULTRA‐PTT) is proposed, utilizing gas bubbles induced by ultrasound to reduce scattering. In‐vivo experiments demonstrate ULTRA‐PTT's superiority in melanoma treatment, suggesting its potential for broader clinical applications beyond superficial tumors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tumor-associated macrophages (TAMs) are involved in tumor progression by promoting epithelial-mesenchymal transition (EMT), tumor cell invasion, migration and angiogenesis. However, in breast cancer, ...the clinical relevance of the TAM infiltration according to distinct histologic locations (intratumoral vs. stromal) and hormone receptor status is unclear. We investigated the significance of the levels of TAM infiltration in distinct histologic locations in invasive breast cancer. We also examined the relationship of the TAM levels with the clinicopathologic features of tumors, expression of EMT markers, and clinical outcomes. Finally, we analyzed the prognostic value of TAM levels according to hormone receptor status. High levels of infiltration of intratumoral, stromal and total TAMs were associated with high histologic grade, p53 overexpression, high Ki-67 proliferation index and negative hormone receptor status. Infiltration of TAMs was also correlated with overexpression of vimentin, smooth muscle actin and alteration of β-catenin. Overall, a high level of infiltration of intratumoral TAMs was associated with poor disease-free survival, and was found to be an independent prognostic factor. In subgroup analyses by hormone receptor status, a high level of infiltration of intratumoral TAM was an independent prognostic factor in the hormone receptor-positive subgroup, but not in the hormone-receptor negative subgroup. Our findings suggest that intratumoral TAMs play an important role in tumor progression in breast cancer, especially in the hormone receptor-positive group, and the level of TAM infiltration may be used as a prognostic factor and even a therapeutic target in breast cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer. This study aims to investigate genomic and clinicopathological characteristics ...of EBVaGC according to the histological pattern. We retrospectively collected 18 specimens of surgically resected EBVaGCs. Whole-exome sequencing was performed for all cases. Moreover, PD-L1 expression and tumor-infiltrating lymphocyte (TIL) percentage were investigated. Among 18 EBVaGCs, 10 cases were of intestinal histology, 3 were of poorly cohesive histology, and the remaining 5 were of gastric carcinoma with lymphoid stroma histology. Whole-exome sequencing revealed that EBVaGCs with intestinal histology harbored pathogenic mutations known to frequently occur in tubular or papillary adenocarcinoma, including
TP53, KRAS
,
FBXW7
,
MUC6
,
ERBB2
,
CTNNB1
, and
ERBB2
amplifications. One patient with poorly cohesive carcinoma histology harbored a
CDH1
mutation. Patients with EBVaGCs with intestinal or poorly cohesive carcinoma histology frequently harbored driver mutations other than
PIK3CA
, whereas those with EBVaGCs with gastric carcinoma with lymphoid stroma histology lacked other driver mutations. Moreover, the histological pattern of EBVaGCs was significantly associated with the levels of TILs (
P
= 0.005) and combined positive score (
P
= 0.027). In conclusion, patients with EBVaGCs with different histological patterns exhibited distinct genetic alteration, PD-L1 expression, and degree of TILs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This study aimed at determining the incidence and clinical implications of HER2 status in primary colorectal cancer (CRC). HER2 status was investigated in two retrospective cohorts of 365 consecutive ...CRC patients (cohort 1) and 174 advanced CRC patients with synchronous or metachronous distant metastasis (cohort 2). HER2 status was determined by performing dual-color silver in-situ hybridization (SISH), mRNA in-situ hybridization (ISH), and immunohistochemistry (IHC). The incidence of HER2 protein overexpression (IHC 2+/3+) was approximately 6% (22 of 365 in cohort 1; 10 of 174 in cohort 2). HER2 gene amplification was observed in 5.8% of the patients from cohort 1 and 6.3% of the patients from cohort 2. HER2 gene amplification was more frequently observed in CRCs located in the rectum than in the right and left colon (P = 0.013 in cohort 1; P = 0.009 in cohort 2). HER2 status, determined by IHC, ISH, and dual-color SISH, was not significantly associated with aggressive CRC behaviour or patients' prognosis in both the cohorts. Of the combined cohort with a total of 539 cases, the concordance rate was 95.5% between dual-color SISH and IHC detection methods. On excluding equivocally immunostained cases (IHC 2+), the concordance rate was 97.7%. HER2 mRNA overtranscription, detected by ISH, significantly correlated with protein overexpression and gene amplification (P<0.001). HER2 gene amplification was identified in a minority of CRC patients with high concordance rates between dual-color SISH and IHC detection methods. Although HER2 status did not predict patients' prognosis, our findings may serve as a basis for future studies on patient selection for HER2 targeted therapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We aimed to evaluate whether a short distal resection margin (< 1 cm) was associated with local recurrence in patients with locally advanced rectal cancer who underwent preoperative ...chemoradiotherapy. Patients with rectal cancer who underwent preoperative chemoradiotherapy followed by curative surgery were divided into two groups based on the distal resection margin (≥ 1 cm and < 1 cm). In total, 507 patients were analyzed. The median follow-up duration was 48.9 months. The 3-year local recurrence rates were 2% and 8% in the ≥ 1 cm and < 1 cm groups, respectively (P < 0.001). Multivariable analysis revealed that a distal resection margin of < 1 cm was a significant risk factor for local recurrence (P = 0.008). Subgroup analysis revealed that a distal resection margin of < 1 cm was not an independent risk factor for local recurrence in the ypT0-1 group. However, among patients with tumor stages ypT2-4, the cumulative 3-year incidences of local recurrence were 2.3% and 9.8% in the ≥ 1 cm and < 1 cm groups, respectively (P = 0.01). A distal resection margin of < 1 cm might influence local recurrence rates in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy, especially in patients with tumor stages ypT2-4.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting ...tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Epstein-Barr virus (EBV)-associated gastric cancer exhibits distinct clinicopathologic characteristics, showing a good response to immune checkpoint inhibitors and a favorable prognosis. However, ...gastric cancer comprising distinct EBV-positive and -negative components in a single mass have been rarely reported, and their detailed genetic characteristics have not yet been investigated. Therefore, we reported the case of gastric cancer exhibiting distinct EBV-positive and -negative areas and further investigated its genetic characteristics.
A 70-year-old man underwent distal gastrectomy for gastric cancer, which was detected during a routine health check-up. EBV-encoded RNA in situ hybridization revealed distinct EBV-positive and -negative components at each other's borders, morphologically consistent with collision tumor. We separately sequenced EBV-positive and -negative tumor areas through whole exome sequencing (WES) with matched normal tissue. Remarkably, both EBV-positive and -negative areas shared pathogenic mutations of ARID1A, KCNJ2, and RRAS2. Furthermore, they shared 92 somatic single nucleotide variants and small insertion or deletion mutations, of which 32.7% and 24.5% are EBV-positive and -negative tumor components, respectively.
WES results suggested that gastric cancer with distinct EBV-positive and -negative tumor components, formerly categorized as a collision tumor, can be clonally related. EBV-negative tumor component might be associated with loss of EBV during tumor progression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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