Source contribution of black carbon aerosol during 2020-2022 at an urban site in Indo-Gangetic Plain.

The extensive emissions of black carbon (BC) from the Indo-Gangetic Plain (IGP) region of India have been well recognized. Particularly, biomass emissions from month-specific crop-residue burning (April, May, October, November) and heating activities (December-February) are considered substantial contributors to BC emissions in the IGP. However, their precise contribution to ambient BC aerosol has not been quantified yet and remains an issue of debate. Therefore, this study aims to fill this gap by quantifying the contribution of these month-specific biomass emissions to ambient BC at an urban site in IGP. This study presents the analysis of BC mass concentrations (MBC) measured for 3 years (2020-2022) in Delhi using an optical photometer i.e., continuous soot monitoring system (COSMOS). A statistical analysis of monthly mean MBC and factors affecting the MBC (ventilation coefficients, air mass back trajectories, fire counts) is performed to derive month-wise contribution due to background concentration, conventional emission, regional transport, crop-residue burning, and heating activities. The yearly mean MBC (5.3 ± 4.7, 5.6 ± 5.0, and 5.3 ± 3.5 µg m-3 during 2020, 2021, and 2022, respectively) remained relatively consistent with repetitive monthly patterns in each year. The peak concentrations were observed from November to January and low concentrations from June to September. Anthropogenic activities contributed significantly to MBC over Delhi with background concentration contributing only 30 % of observed MBC. The percentage contribution of emissions from crop-residue burning varied from 15 % (May) to 37 % (November), while the contribution from heating activities ranged from 25 % (December) to 39 % (January). This source quantification study highlights the significant impact of month-specific biomass emissions in the IGP and can play a vital role in better management and control of these emissions in the region.

Black carbon scavenging by low-level Arctic clouds.

Black carbon (BC) from anthropogenic and natural sources has a pronounced climatic effect on the polar environment. The interaction of BC with low-level Arctic clouds, important for understanding BC deposition from the atmosphere, is studied using the first long-term observational data set of equivalent black carbon (eBC) inside and outside of clouds observed at Zeppelin Observatory, Svalbard. We show that the measured cloud residual eBC concentrations have a clear seasonal cycle with a maximum in early spring, due to the Arctic haze phenomenon, followed by cleaner summer months with very low concentrations. The scavenged fraction of eBC was positively correlated with the cloud water content and showed lower scavenged fractions at low temperatures, which may be due to mixed-phase cloud processes. A trajectory analysis revealed potential sources of eBC and the need to ensure that aerosol-cloud measurements are collocated, given the differences in air mass origin of cloudy and non-cloudy periods.

Physical and chemical properties of PM1 in Delhi: A comparison between clean and polluted days.

Considering the significance of PM1 aerosol in assessing health impacts of air pollution, an extensive analysis of PM1 samples collected at an urban site in Delhi is presented in this study. Overall, PM1 contributed to about 50 % of PM2.5 mass which is alarming especially in Delhi where particle mass loadings are usually higher than prescribed limits. Major portion of PM1 consisted of organic matter (OM) that formed nearly 47 % of PM1 mass. Elemental carbon (EC) contributed to about 13 % of PM1 mass, whereas SO42- (16 %), NH4+ (10 %), NO3- (4 %) and Cl- (3 %) were the major inorganic ions present. Sampling was performed in two distinctive campaign periods (in terms of meteorological conditions and heating (fire) activities), during the year 2019, each spanning two-week time, i.e. (i) September 3rd-16th (clean days), and (ii) November 22nd-December 5th (polluted days). Additionally, PM2.5 and black carbon (BC) were measured simultaneously for subsequent analysis. The 24-h averaged mean concentrations of PM2.5 and BC during clean days (polluted days) were 70.6 ± 26.9 and 3.9 ± 1.0 µg m-3 (196 ± 104 and 7.6 ± 4.1 µg m-3), respectively, which were systematically lower (higher) than that of the annual mean (taken from studies conducted at same site in 2019) of 142 and 5.7 µg m-3, respectively. Changes in characteristic ratios (i.e., organic carbon (OC)/elemental carbon (EC) and K+/EC) of chemical species detected in PM1 show an increase in biomass emissions during polluted days. Increase in biomass emission can be attributed to increase in heating practices (burning of biofuels such as wood logs, straw, and cow-dung cake) in- and around- Delhi because of fall in temperature during second campaign. Furthermore, a significant increase in NO3- fraction of PM1 is observed during second campaign which shows fog processing of NOX due to conducive meteorological conditions in winters. Also, comparatively stronger correlation of NO3- with K+ during second campaign (r = 0.98 as compared to r = 0.5 during first campaign) suggests the increased heating practices to be a contributing factor for increased fraction of NO3- in PM1. We observed that during polluted days, meteorological parameters such as dispersion rate also played a major role in intensifying the impact of increased local emissions due to heating activities. Apart from this, change in the direction of regional emission transport to study site and the topology of Delhi are the possible reasons for the elevated pollution level, especially PM1 during winter in Delhi. This study also suggests that black carbon measurement techniques used in current study (optical absorbance with heated inlet and evolved carbon techniques) can be used as reference techniques to determine the site-specific calibration constant of optical photometers for urban aerosol.

Changes in black carbon and PM2.5 in Tokyo in 2003-2017.

Black carbon (BC) particles cause adverse health effects and contribute to the heating of the atmosphere by absorbing visible solar radiation. Efforts have been made to reduce BC emissions, especially in urban areas; however, long-term measurements of BC mass concentration (MBC) are very limited in Japan. We report MBC measurements conducted in Tokyo from 2003 to 2017, showing that MBC decreased by a factor of 3 from 2003 to 2010 and was stable from 2010 to 2017. Fine particulate concentrations (PM2.5) decreased by a much smaller factor during 2003-2010. The diurnal variations of BC size distributions suggest that the BC in Tokyo originates mainly from local sources, even after 2010. Our three-dimensional model calculations show that BC from the Asian continent contributes a small portion (about 20%) of the annual average MBC in the Kanto region of Japan, which includes Tokyo. This indicates that continued reduction of BC emissions inside Japan should be effective in further decreasing MBC.

Anthropogenic combustion iron as a complex climate forcer.

Atmospheric iron affects the global carbon cycle by modulating ocean biogeochemistry through the deposition of soluble iron to the ocean. Iron emitted by anthropogenic (fossil fuel) combustion is a source of soluble iron that is currently considered less important than other soluble iron sources, such as mineral dust and biomass burning. Here we show that the atmospheric burden of anthropogenic combustion iron is 8 times greater than previous estimates by incorporating recent measurements of anthropogenic magnetite into a global aerosol model. This new estimation increases the total deposition flux of soluble iron to southern oceans (30-90 °S) by 52%, with a larger contribution of anthropogenic combustion iron than dust and biomass burning sources. The direct radiative forcing of anthropogenic magnetite is estimated to be 0.021 W m-2 globally and 0.22 W m-2 over East Asia. Our results demonstrate that anthropogenic combustion iron is a larger and more complex climate forcer than previously thought, and therefore plays a key role in the Earth system.

Anthropogenic iron oxide aerosols enhance atmospheric heating.

Combustion-induced carbonaceous aerosols, particularly black carbon (BC) and brown carbon (BrC), have been largely considered as the only significant anthropogenic contributors to shortwave atmospheric heating. Natural iron oxide (FeOx) has been recognized as an important contributor, but the potential contribution of anthropogenic FeOx is unknown. In this study, we quantify the abundance of FeOx over East Asia through aircraft measurements using a modified single-particle soot photometer. The majority of airborne FeOx particles in the continental outflows are of anthropogenic origin in the form of aggregated magnetite nanoparticles. The shortwave absorbing powers (Pabs) attributable to FeOx and to BC are calculated on the basis of their size-resolved mass concentrations and the mean Pabs(FeOx)/Pabs(BC) ratio in the continental outflows is estimated to be at least 4-7%. We demonstrate that in addition to carbonaceous aerosols the aggregate of magnetite nanoparticles is a significant anthropogenic contributor to shortwave atmospheric heating.

A key process controlling the wet removal of aerosols: new observational evidence.

The lifetime and spatial distributions of accumulation-mode aerosols in a size range of approximately 0.05-1 µm, and thus their global and regional climate impacts, are primarily constrained by their removal via cloud and precipitation (wet removal). However, the microphysical process that predominantly controls the removal efficiency remains unidentified because of observational difficulties. Here, we demonstrate that the activation of aerosols to cloud droplets (nucleation scavenging) predominantly controls the wet removal efficiency of accumulation-mode aerosols, using water-insoluble black carbon as an observable particle tracer during the removal process. From simultaneous ground-based observations of black carbon in air (prior to removal) and in rainwater (after removal) in Tokyo, Japan, we found that the wet removal efficiency depends strongly on particle size, and the size dependence can be explained quantitatively by the observed size-dependent cloud-nucleating ability. Furthermore, our observational method provides an estimate of the effective supersaturation of water vapour in precipitating cloud clusters, a key parameter controlling nucleation scavenging. These novel data firmly indicate the importance of quantitative numerical simulations of the nucleation scavenging process to improve the model's ability to predict the atmospheric aerosol burden and the resultant climate forcings, and enable a new validation of such simulations.

Clinical Benefits of Memantine Treatment for Alzheimer's Disease in the Okayama Memantine Study II (OMS II).

The clinical benefits of memantine, depending on the baseline cognitive and affective conditions in real world dementia clinics, have not been completely examined. We performed the "Okayama Memantine Study II (OMS II)" to retrospectively evaluate the clinical effects of memantine monotherapy (n = 38) in Alzheimer's disease (AD) patients using seven batteries to assess dementia at the baseline, at 3, 6, and 12 months. Additionally, we divided 163 AD patients treated with memantine into two subgroups depending on the baseline cognitive score of the Mini-Mental State Examination (MMSE): the MMSE <15 group (n = 36) and the baseline MMSE ≥15 group (n = 127). We also analyzed 71 AD patients based on the baseline behavioral and psychological symptoms of dementia (BPSD) severity using Abe's BPSD score (ABS). Memantine monotherapy maintained cognitive functions until 6 months of treatment, but showed a decrease at 12 months ( *p <  0.05 versus baseline). However, memantine monotherapy greatly improved BPSD symptoms until 12 months ( *p <  0.05,  **p <  0.01) and maintained other affective functions as well as the activity of daily living. Memantine treatment showed similar effects, regardless of the baseline cognitive functions, but showed better effects on ABS for higher baseline cognitive functions. Memantine treatment greatly improved ABS depending on baseline BPSD severity. Our present OMS II showed that memantine monotherapy improved BPSD until 12 months. The higher baseline cognitive subgroup (MMSE ≥15) and the worse baseline BPSD subgroup were expected to show better effects with memantine.

Gastric mixed adenoneuroendocrine carcinoma with thyroid transcription factor-1-positive neuroendocrine component.

Small cell carcinoma of the stomach, which is considered synonymous with neuroendocrine carcinoma, is rare. We encountered a case of mixed adenoneuroendocrine carcinoma. Gastrointestinal endoscopy revealed a type 0 IIa + IIc lesion in the stomach. Biopsy suggested well-differentiated adenocarcinoma. Endoscopic submucosal dissection was performed and gastric cancer comprising both well to moderately differentiated adenocarcinoma within the mucous membrane and small cell carcinoma invading to the submucosa with accompanying vessel invasion was found. Mixed adenoneuroendocrine carcinoma was diagnosed and the small cell carcinoma was thyroid transcription factor-1 positive. No tumor lesions were apparent in other organs, so distal gastrectomy and lymph node dissection were performed. Lymph node metastases were not observed. The patient is currently alive without recurrence. Thyroid transcription factor-1-positive gastric neuroendocrine carcinoma is very rare, and the thyroid transcription factor-1-positive rate may contribute to the prediction of prognosis and treatment selection. Accumulation of cases is thus very important.

[A case of recurrent breast cancer with brain metastases successfully treated with vinorelbine and anastrozole after multiple chemo-endocrine therapies].

We report a case of recurrent hormone receptor-positive breast cancer with brain metastases that showed good response to vinorelbine(VNR)and anastrozole(ANA). A 49-year-old woman with a history of left breast cancer had initially undergone modified radical mastectomy, but was diagnosed with lung metastases 8 years postoperatively. Despite treatment with docetaxel and tamoxifen, multiple brain metastases were detected 10 years postoperatively. To achieve prompt improvement of neurological symptoms, surgical resection was performed for two large brain foci. Stereotactic radiosurgery using a gamma- knife was applied for the remaining multiple brain metastases. Histological examination identified the brain tumors as estrogen receptor-positive, HER2-negative metastatic breast cancer. Despite the use of cyclophosphamide, adriamycin and 5- fluorouracil(CAF therapy)and capecitabine, brain metastases recurred twice along with pleuritis carcinomatosis and bone metastasis. In addition to gamma-knife re-treatment, therapy was started with VNR and ANA. All metastatic sites including brain showed a good response to therapy with few adverse reactions, and no recurrence has been observed over 3 years.

Sigmoid colon perforation induced by the vascular type of Ehlers-Danlos syndrome: report of a case.

The vascular type of Ehlers-Danlos syndrome (vEDS) is a rare inherited disease of the connective tissues, and is caused by abnormal type III collagen resulting from heterogeneous mutations of the type III collagen COL3A1 gene. We herein report the case of a vEDS patient who developed a sigmoid colon perforation and was given a definitive diagnosis by a genetic and biomolecular assay. The patient demonstrated clinical manifestations caused by tissue weakness such as frequent pneumothorax events and a detached retina. During the operation, we noticed easy bruising and thin skin with visible veins on the patient's abdominal wall. Finally, a diagnosis was confirmed by the reduction of type III collagen synthesis and by the identification of a mutation in the gene for type III collagen. We conclude that it is difficult to diagnose a vEDS patient without clinical experiences and specialized genetic methods. Furthermore, all organs must be treated gently during therapy, because the tissues of vEDS patients are extremely fragile.

Placement of an expandable metallic stent improves the efficacy of chemoradiotherapy for pancreatic cancer with malignant portal vein stenosis or obstruction.

BACKGROUND: Advanced or recurrent pancreatic cancer can sometimes cause obstruction or stenosis of the portal vein (PV), resulting in various symptoms of portal hypertension (PH), such as ascites, pancytopenia, hemorrhagic tendencies and liver dysfunction. We placed an expandable metallic stent into the PV to improve PH-associated complications and liver function. The placement of the PV stent was beneficial for administering chemotherapeutic agents and radiotherapy (RT) safely, and resulted in an improved response rate (RR) and survival. PATIENTS AND METHODS: In the present study, 14 patients with malignant portal obstruction due to advanced or recurrent pancreatic cancer received PV stent placement to manage their PH-associated symptoms. After a mini-laparotomy at the ileocecal region, the ileocecal vein was cut and an expandable metallic stent (6-8 mm in diameter and 6-8 cm in length) was inserted into the PV under image roentgenography. After placement of the PV stent, the patients received anti-coagulation treatment with heparin and biaspirin for 1-3 months. All patients received chemotherapy with UFT, cyclophosphamide (CPA) and gemcitabine (GEM), and 11 patients also received RT. RESULTS: The RR was 43% (3 complete (CR), 3 partial (PR), 3 stable disease (SD), and 5 progressive disease (PD)), and the mean survival times (MST) after the initiation of therapy or placement of the PV-stent were 12.6 and 9.5 months, respectively, while the 1-year survival rates were 54.5% and 35.1%, respectively. In the 3 CR patients, 2 died of carcinomatous ascites 13 and 21 months later, and 1 is still disease free. In the PR and SD patients, pain and PH-associated symptoms such as ascites and hyperglycemia were also improved. CONCLUSION: The placement of a PV stent is beneficial for improving PH-associated symptoms as well as facilitating chemo-RT and the efficacy of therapy.

High incidence of synchronous or metachronous breast cancer in patients with malignant and benign thyroid tumor or tumor-like disorders.

BACKGROUND: Although many reports indicated an association between thyroid diseases and breast cancer, such an association still remains controversial. The present study was aimed to clarify the association of thyroid diseases with the breast cancer incidence. In the patients with benign and malignant thyroid tumor or tumor-like disorders, the incidence of other malignancies was surveyed, and the frequency of thyroid cancer in patients with breast cancer was also surveyed. PATIENTS AND METHODS: Between 1982 and 2005, a total of 201 female patients received surgery for tumor or tumor-like disorders, including 65 carcinoma, 68 adenoma, 61 adenomatous goiter and 7 chronic thyroiditis cases. Their outcomes were surveyed in December 2006. Furthermore, during the same periods, 340 female patients underwent breast cancer surgery and their outcomes were also surveyed in December 2006. RESULTS: The overall incidence rate of breast cancer was 16.4% (33/201) in the patients, who received thyroid surgeries and was much higher than other malignancies: 2.0% gastric cancer, 1.0% uterine and colorectal cancer. The incidence rate of breast cancer in each disease was 13.8% for thyroid cancer, 16.2% for adenoma and 21.3% for adenomatous goiter, but no incidence for chronic thyroiditis. On the other hand, in the patients with breast cancer during the same period in our department, the frequency of thyroid cancer was only 2.1% (7/340). CONCLUSION: It appears that thyroid cancer, adenoma and adenomatous goiter were associated with the risk of breast cancer, but chronic thyroiditis was not related.

Cyclophosphamide augments the anti-tumor efficacy of uracil and tegafur by inhibiting dihydropyrimidine dehydrogenase.

The present study assesses the effects of neo-adjuvant chemotherapy (NAC) with uracil and tegafur (UFT) alone vs UFT plus cyclophosphamide (CPA), on the activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in breast cancer tissues. Breast cancer patients were randomly assigned to 3 groups; the control (no-treatment) group (n=13), the UFT (5-8 mg/kg/day) alone group (n=10) and the UFT plus CPA (1 mg/kg/one day interval) (UC) group (n=9), and they received NAC for 2-4 weeks. A total of 32 invasive ductal breast carcinomas were used to assay for TS and DPD activity. There were no statistically significant differences in tumor size or stage classification between the 3 groups. The DPD activity was inversely and significantly correlated with the tumor size and pT, but the TS activity was not correlated with these clinicopathological factors. The TS activity was decreased by NAC with UFT, and the addition of CPA resulted in an increased inhibition of TS activity. In contrast, DPD activity was increased by NAC with UFT administration, but its increased activity was significantly inhibited by the addition of CPA. Multiple regression analyses demonstrated that the total dose of UFT was a significant variable for inhibiting TS activity, and that CPA was a significant variable for inhibiting DPD activity. The DPD activity increased by UFT can be inhibited by CPA, and this may represent one of the possible mechanisms responsible for the anti-tumor activity of 5-FU or its derivatives as enhanced by CPA.

Immunohistochemical expression of HER-1 and HER-2 in extrahepatic biliary carcinoma.

The clinicopathological significance of HER-1- and HER-2-overexpressions (OE) (HercepTest score 2+ or 3+) in biliary cancer and their relationship to the efficacy of adjuvant chemotherapy (ACT) were assessed. In 72 biliary cancer (28 gallbladder and 44 bile duct cancer), HER-1 and HER-2 were stained immunohistochemically in formalin-fixed, paraffin-embedded specimens. The ACT included uracil and tegafur (UFT)-based chemotherapies. Out of the 72 cancer, OE was observed in 31 specimens (43%) for HER-1 and 47 (65%) for HER-2. However, their OEs were not correlated with each other. HER-2-OE was inversely correlated with the clinical stage (p=0.0482). HER-1-OE was correlated with distant metastasis (p=0.0263), but not with the clinical stage. Neither the OE of HER-1 or HER-2, nor their co-expression, showed any significant effect in term of patient survival. In the HER-1-OE (-) patients, the survival rate of the ACT group was significantly higher than that of the surgery-alone (SA) group (p=0.0423), but in the HER-1-OE (+) patients, there was no statistical difference in survival rate between the ACT and the SA group. In contrast, HER-2-OE had no significant effect on the efficacy of ACT. Multivariate analysis also demonstrated that the histological grade and ACT were significant variables, but T, N, M and HER-1 and HER-2 were not significant variables. In conclusion, neither HER-1-OE or HER-2-OE were prognostic factors of the biliary cancer. However, HER-1-OE may be a useful marker for the indication of ACT.

[Pancreatic acinar cell carcinoma successfully treated with combination of oral TS-1 and intra-arterial cisplatin].

Pancreatic acinar cell carcinomas are rare, and little is reported on their chemotherapy. We report a 49-year old male patient with pancreatic acinar cell carcinoma and multiple liver metastases, which responded to oral TS-1 and hepatic arterial infusion of cisplatin. The patient underwent a partial hepatectomy, MCT abrasions and excision of the pancreatic tumor. Postoperative pathological studies revealed metastases of acinar cell carcinoma to the liver and lymph nodes; the primary lesion was undetermined. After surgery, the patient was treated with hepatic arterial infusion of cisplatin and oral TS-1. Metastatic tumors completely disappeared, and serum lipase decreased to normal levels. Abdominal CT one year after surgery revealed a pancreatic body tumor, which was surgically removed. Pathological studies showed primary pancreatic acinar cell carcinoma, while previous metastases remained under control. To summarize, TS-1 and cisplatin can be effective treatments for pancreatic acinar cell carcinomas.

Immunohistochemical expression of receptor-tyrosine kinase c-kit protein and TGF-beta1 in invasive ductal carcinoma of the pancreas.

BACKGROUND: The receptor tyrosine kinase c-kit is known to play an important role in the progression of gastrointestinal stromal tumors, but its biological significance in other solid malignancies is unclear. Recent publications have suggested a regulatory role for TGF-beta1 in c-kit-mediated cell growth. The present study assessed the clinicopathological significance of c-kit protein (KIT) and TGF-beta1 expression in resectable invasive ductal carcinomas (IDCs) of the pancreas. PATIENTS AND METHODS: This study included 91 pancreatic IDC patients who received a pancreatectomy between 1982 and 2003. The expression of KIT and TGF-beta1 was analyzed by immunohistochemistry. RESULTS: KIT and TGF-beta1 were expressed in 77% (70/91) and 59% (54/91) of the IDC, respectively. The expression of KIT was not correlated with that of TGF-beta1. TGF-beta1 expression correlated inversely with nodal involvement, but KIT expression did not correlate with any clinicopathological factors. KIT expression had no significant influence on the survival of the patients, whereas the survival rate of TGF-beta1 (+) IDC patients was significantly higher than that of TGF-beta1 (-) IDC patients. Co-expression analysis of KIT and TGF-beta1 indicated that, in patients with KIT (+) IDC, the TGF-beta1 (+) group showed a significantly better survival rate than the TGF-beta1 (-) group. Neither KIT expression nor TGF-beta1 expression had a significant effect on the efficacy of adjuvant chemotherapy (ACT). In multivariate analysis, TGF-beta1 expression was one of the significant variables for survival in IDC patients overall, but KIT expression was not. CONCLUSION: TGF-beta1 expression is suggested to have a significant influence on c-kit-mediated cell proliferation in human pancreatic IDCs.

Phase II study on low dose gemcitabine plus oral chemotherapy with uracil-tegafur and cyclophosphamide in combination with radiotherapy against recurrent and advanced pancreatic cancer.

The present study assessed the anti-tumor effects and clinical benefits of intravenous (i.v.) or intra-arterial (i.a.) gemcitabine (GEM) at low dose plus oral chemotherapy with uracil-tegafur (UFT) and cyclophosphamide (CPA) in combination with radiotherapy (RT) against recurrent and advanced pancreatic cancers. A total of 22 patients with 15 advanced or 7 recurrent pancreatic cancer were enrolled. The target lesions included 15 primary tumors, 9 liver metastases, 3 local recurrences, 1 lung metastasis and 1 pleural effusion. The patients were each given GEM at 200-400 mg weekly or biweekly, UFT at 300 mg/day daily and CPA at 50 mg/day every other day in combination with RT at a total dose of 40-60 Gy. The primary efficacy measures were the overall response rate (RR) and survival. Furthermore, the clinical benefit response (CBR) was classified by measuring the pain intensity, analgesic consumption, Karnofsky performance status and body weight. The regimen was well tolerated, and the major side effects included anorexia, general malaise and myelo-suppression. In each case, dose reduction was effective in resolving these side effects. The dose limiting side effect was thrombocytopenia. Eleven patients received i.v. GEM alone, 6 patients received i.a. GEM alone and 5 patients received both. The objective responses were evaluated in all patients, and the overall RR was 27% (2 complete responses, 4 partial responses, 6 stable diseases and 10 progressive diseases). A CBR was experienced in 22.7% of the patients. The mean survival period was 10.6 months (2-20 months), and the 1-year survival rate was 42.2%. There were no differences in RR and survival among the different administration methods of GEM. In conclusion, i.v. or i.a. GEM at low dose, UFT and CPA in combination with RT is a well-tolerated regimen with beneficial clinical efficacy, and is worthy of further study.

Expression of retinoblastoma and p53 pathway-related proteins in resectable invasive ductal carcinoma of the pancreas: potential cooperative effects on clinical outcome.

BACKGROUND: The retinoblastoma protein (RB) is an important cell cycle regulator. RB also plays an important role in the regulation of apoptosis, which is mediated by interaction of p53 signaling mediators. The present study was designed to assess the clinicopathological significance of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax) expression in resectable invasive ductal carcinoma (IDC) of the pancreas. MATERIALS AND METHODS: The present study included 79 pancreatic IDC patients, who received surgery between 1982 and 2002. The expression of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax) were analyzed by immunohistochemistry. RESULTS: RB was expressed in 45 (57%) of the 79 patients. RB expression correlated significantly with histological grade and grade of nodal involvement. The positive rate of p53, p21WAF1/CIP1 and Bax expression was 49%, 48% and 67%, respectively. RB expression alone did not have a significant effect on patient survival. However, coexpression analysis of RB and p53 pathway-related proteins indicated that, in the patients with RB (+) IDC, the p21WAF1/CIP1 (+) group had a significantly higher survival rate than the p21WAF1/CIP1 (-) group. On the other hand, in the patients with RB (-) IDC, the Bax (+) group had a significantly higher survival rate than the Bax (-) group. Multivariate analysis indicated that, in the RB (-) group, pTNM stage, adjuvant chemotherapy and Bax expression were significant variables. CONCLUSION: The evaluation of RB expression combined with the mediators of the p53 pathway, p21WAF1/CIP1 and Bax, may provide more accurate information regarding clinical outcome, beyond that which is provided by RB expression alone.

[A case of liver metastases of breast cancer successfully treated by combination chemotherapy using hepatic arterial infusion of docetaxel and systemic administration of trastuzumab].

A 43-year-old woman underwent breast-conserving therapy for right breast cancer with multiple liver metastases (pT3N3aM1, stage IV, ER (-), PgR (-), HER2 (3+)), in November, 2002. Following surgery, she received combination chemotherapy using hepatic arterial infusion of docetaxel and systemic administration of trastuzumab weekly. During therapy, no serious side effects and only grade 1 nausea were observed; after 3 courses, therapy was safely continued on an outpatient basis. Metastatic liver tumors responded to the treatment, and they completely disappeared on an abdominal CT 5 months later. In addition, all elevated tumor markers in serum decreased to the normal range. No new metastatic or recurrent lesions were found 14 months after surgery. We conclude that this combination chemotherapy is safe and may be very useful for the treatment of breast cancer patients with liver metastasis.