Potential antioxidant and antiproliferative activities of a hot-water extract from the root of Tonh khidum

In this study, for the first time, the possible antioxidant and antiproliferative activities of a hot-water extract (TW100) from the root of Tonh khidum (Actinidia kolomikta Maxim) were examined in vitro. Total phenolic compound, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and superoxide dismutase (SOD)-like activity assays were utilized to investigate its antioxidant activity. As a result, TW100 showed a strong antioxidant activity. The total phenolic content of TW100 was 143 μg gallic acid equivalents/mg. The SOD-like activity of TW100 was 666,667 U/g extract, and the DPPH radical-scavenging activity was 129 μg/ml at EC(50) which was one third of vitamin E (40 μg/ml). The antiproliferative effects and ability of the extracts to induce apoptosis were studied in vitro using human cervical cancer ME-180 cells. Results showed that TW100 inhibited the proliferation of ME-180 cells in a dose- and time-dependent manner except at a low concentration (10 μg/ml) with an EC(50) at 24, 48 and 72 h of 36.28, 30.55 and 29.78 μg/ml, respectively. TW100 also induced apoptosis as determined by a nuclear fragmentation assay and an analysis of flow cytometry. In conclusion, the hot-water extract from the root of Tonh khidum possesses potential antioxidant and antiproliferative activities.     

Local recurrence after mesorectal excision for rectal cancer.

AIMS: Controversy still exists about the optimal surgical treatment of rectal cancer. The main purpose of the present study was to compare local recurrence (LR) rates after mesorectal excision (ME) and conventional surgery (CS) technique. METHODS: All rectal cancer patients from a defined catchment area were included. Outcome after ME in the period 1993-1999 (n=161) was compared with the outcome after CS (n=217) in the period 1983-1992. Partial ME (PME) was the routine in upper, and total ME the routine in mid- and low rectal cancer. The follow-up programmes were identical, and the median observation times very similar (37 and 38 months) in the two periods. Five-year actuarial LR rate and survival were estimated using the Kaplan-Meier method, and adjustment for prognostic factors was performed with Cox regression analysis. RESULTS: Total LR rate after R0 resection was 7.7% crude and 9% 5 year actuarial in the ME period, as compared with 16.0% crude and 24% actuarial in the CS period (P=0.02). Cox regression analyses confirmed these differences with a hazard ratio of 0.40 for ME vs CS (P=0.02). Isolated LR rate was 2% after ME and 8% after CS. Five-year actuarial total LR rate after rectal resection with curative intent was 11% after ME and 27% after CS (P<0.01). Actuarial total LR rate after PME was 6%, and none of these patients developed isolated LR. CONCLUSION: Standardization of surgical technique and application of ME resulted in a significant reduction of LRs. LR rate was low after PME, indicating that this procedure is adequate in upper rectal cancer. Copyright Harcourt Publishers Limited.     

Comparison of ThinPrep and conventional smears in salivary gland fine-needle aspiration biopsies

BACKGROUND: ThinPrep (TP) cytology for evaluation of nongynecological specimens is being increasingly used. There are few studies comparing TP with conventional smears (CS) in salivary gland (SG) fine-needle aspiration biopsies (FNAB). This study compares diagnostic accuracy and morphology of TP and CS in SG FNABs. METHODS: The authors retrospectively reviewed 98 satisfactory SG FNABs with both TP and CS. All cases had surgical resection. CS and TP slides were assessed for multiple morphological parameters, as well as the ability to make the diagnosis. Chi-square analysis was performed to compare CS and TP. RESULTS: An accurate diagnosis was rendered more commonly with CS compared with TP (57% versus 42%; P = .032), whereas the unsatisfactory rate was greater with TP compared with CS (19% versus 9%; P = .041). The error (4%) and indeterminate (35%) rates for TP were similar to CS. The diagnostic yield was greater for cellular cases, which were more frequent with CS compared with TP, than for cases of low cellularity; the diagnostic yield of cellular TP cases and cellular CS cases was similar. Artifacts (crush, air drying, obscuring blood) were more frequent (12%, 13%, and 27% versus 2%, 0%, and 1%; P 相似文献   

Immunohistochemical demonstration of cytokeratin is useful for detecting micrometastatic foci from gallbladder carcinoma in regional lymph nodes

BACKGROUND: The histological detection of lymph node metastasis in patients with gallbladder carcinoma is of major prognostic significance. However, it may be difficult to identify nodal involvement by conventional pathological examination of hematoxylin-eosin (HE)-stained sections when metastases are of microscopic size. In the present study, an attempt was made to detect lymph node metastasis precisely from gallbladder carcinoma, even by low-power microscopic examination, using immunohistochemistry with an anti-cytokeratin antibody. METHODS: A total of 431 lymph node specimens dissected during surgery from 33 patients with carcinoma of the gallbladder were investigated. A pair of mirror-image sections were obtained from each of the dissected lymph nodes and then stained using standard HE and immunohistochemical methods utilizing a monoclonal antibody against cytokeratin 7. The HE- and immunohistochemically stained sections were examined for the presence of tumor cells using light microscopy. RESULTS: All 78 lymph nodes from 12 patients with early gallbladder carcinoma were negative for both HE- and cytokeratin-positive cancer cells. Of 353 lymph nodes from 21 patients with advanced gallbladder carcinoma, HE staining showed that 98 were metastasis-positive. Among these 98 lymph nodes, 95 (97%) proved to be positive for metastasis based on cytokeratin immunostaining. On the other hand, the remaining 255 lymph nodes were cancer-free on the basis of HE staining results. Of the 255 HE-negative lymph nodes, seven (2.7%) were found to be positive for micrometastasis on the basis of cytokeratin staining. CONCLUSIONS: Cytokeratin staining of dissected lymph nodes is a useful new diagnostic tool for detecting micrometastatic foci in regional lymph nodes of patients with gallbladder carcinoma.     

Comparison of ThinPrep and conventional smears in salivary gland fine‐needle aspiration biopsies

BACKGROUND

ThinPrep (TP) cytology for evaluation of nongynecological specimens is being increasingly used. There are few studies comparing TP with conventional smears (CS) in salivary gland (SG) fine‐needle aspiration biopsies (FNAB). This study compares diagnostic accuracy and morphology of TP and CS in SG FNABs.

METHODS

The authors retrospectively reviewed 98 satisfactory SG FNABs with both TP and CS. All cases had surgical resection. CS and TP slides were assessed for multiple morphological parameters, as well as the ability to make the diagnosis. Chi‐square analysis was performed to compare CS and TP.

RESULTS

An accurate diagnosis was rendered more commonly with CS compared with TP (57% versus 42%; P = .032), whereas the unsatisfactory rate was greater with TP compared with CS (19% versus 9%; P = .041). The error (4%) and indeterminate (35%) rates for TP were similar to CS. The diagnostic yield was greater for cellular cases, which were more frequent with CS compared with TP, than for cases of low cellularity; the diagnostic yield of cellular TP cases and cellular CS cases was similar. Artifacts (crush, air drying, obscuring blood) were more frequent (12%, 13%, and 27% versus 2%, 0%, and 1%; P ≤ .006) in CS compared with TP. Although fragmentation was greater and nuclear detail was better in TP (P ≤ .03), cell size was larger in CS (P = .002). A specific diagnosis of pleomorphic adenoma (PA) was more frequently rendered with CS compared with TP (83% versus 63%; P = .045). PA stroma was more abundant, and an epithelial‐stromal interface (ESI) was more frequent in CS compared with TP (ESI, 76% versus 38%; P ≤ .001).

CONCLUSIONS

There are morphological differences between TP and CS in SG FNABs, especially with respect to stromal appearance. Although CS appears to be preferable to TP in the diagnosis of PA overall, CS and TP have equivalent diagnostic yield in highly cellular cases. Complementary use of both TP and CS preparations to achieve optimal diagnostic yield is recommended, given the artifacts of some CS and the not infrequent unsatisfactory nature of 1 preparation alone. Cancer (Cytopathol) 2007. © 2007 American Cancer Society.     

The antiemetic activity of high-dose metoclopramide and high-dose alizapride in combination with lorazepam in patients receiving cancer chemotherapy. A prospective, randomized, double-blind study

The antiemetic efficacy of metoclopramide and lorazepam (MTC + L) versus alizapride and lorazepam (ALZ + L) was compared in 100 patients receiving chemotherapy, in a prospective randomized double-blind study. In highly emetogenic (HE) regimen (including platinum) patients received MTC 1 mg/kg or ALZ 3 mg/kg x 4 doses, and lorazepam 2.5 mg 30 min before therapy. In moderately emetogenic (ME) regimen patients received MTC 0.5 mg/kg or ALZ 1.5 mg kg x 3 doses, and lorazepam 2.5 mg 30 min before therapy. In both HE and ME regimen groups there was no statistically significant difference between MTC + L and ALZ + L treatments as regards the number of vomiting episodes, the duration of emesis and nausea, the intensity of nausea and side effects, but a statistically significant difference between treatments was found in the HE group where MTC-L was superior to ALZ + L in obtaining complete protection from vomiting (37 vs 11%, p = 0.05). No significant difference in side effects was observed.     

Anti-cancer analogues ME-143 and ME-344 exert toxicity by directly inhibiting mitochondrial NADH: ubiquinone oxidoreductase (Complex I)

Isoflavonoids have been shown to inhibit tumor proliferation and metastasis by activating cell death pathways. As such, they have been widely studied as potential therapies for cancer prevention. The second generation synthetic isoflavan analogues ME-143 and ME-344 also exhibit anti-cancer effects, however their specific molecular targets have not been completely defined. To identify these targets, we examined the effects of ME-143 and ME-344 on cellular metabolism and found that they are potent inhibitors of mitochondrial oxidative phosphorylation (OXPHOS) complex I (NADH: ubiquinone oxidoreductase) activity. In isolated HEK293T mitochondria, ME-143 and ME-344 reduced complex I activity to 14.3% and 28.6% of control values respectively. In addition to the inhibition of complex I, ME-344 also significantly inhibited mitochondrial complex III (ubiquinol: ferricytochrome-c oxidoreductase) activity by 10.8%. This inhibition of complex I activity (and to a lesser extent complex III activity) was associated with a reduction in mitochondrial oxygen consumption. In permeabilized HEK293T cells, ME-143 and ME-344 significantly reduced the maximum ADP-stimulated respiration rate to 62.3% and 70.0% of control levels respectively in the presence of complex I-linked substrates. Conversely, complex II-linked respiration was unaffected by either drug. We also observed that the inhibition of complex I-linked respiration caused the dissipation of the mitochondrial membrane potential (ΔΨ_m). Blue native (BN-PAGE) analysis revealed that prolonged loss of ΔΨ_m results in the destabilization of the native OXPHOS complexes. In particular, treatment of 143B osteosarcoma, HeLa and HEK293T human embryonic kidney cells with ME-344 for 4 h resulted in reduced steady-state levels of mature complex I. Degradation of the complex I subunit NDUFA9, as well as the complex IV (ferrocytochrome c: oxygen oxidoreductase) subunit COXIV, was also evident. The identification of OXPHOS complex I as a target of ME-143 and ME-344 advances our understanding of how these drugs induce cell death by disrupting mitochondrial metabolism, and will direct future work to maximize the anti-cancer capacity of these and other isoflavone-based compounds.     

Unmet needs in the international neuroendocrine tumor (NET) community: Assessment of major gaps from the perspective of patients,patient advocates and NET health care professionals

Due to the increasing incidence and prevalence of neuroendocrine tumors (NETs), there is a need to assess any gaps in awareness and care. A survey was undertaken in 2017 to identify perceived unmet needs from the perspectives of patients/families, patient advocates and health care professionals (HCPs). The survey consisted of 33–37 questions (depending on type of respondent) across four areas: information, care, treatments and research. In total, 443 participants from 26 countries responded: 338 patients/families, 35 advocates and 70 HCPs. Perceived unmet needs regarding provision of information at diagnosis differed between groups. While 59% of HCPs believed they provided sufficient information, informational needs were mostly/fully met for only 30% of patients and 18% of advocates. Additionally, 91% of patients and 97% of advocates felt that patients had to search for information themselves. Availability of Gallium-68-Dotatate PET/CT scan was limited for the majority of patients (patients: 73%; advocates: 85%; HCP: 86%), as was access to treatments, particularly peptide receptor radionuclide therapy (patients: 42%; advocates: 95%; HCPs: 77%). All groups felt that standards of care, including psychological needs and diagnosis of mental health, were not fully met. Although about two-thirds of patients were managed by a multidisciplinary team, 14% of patients reportedly did not have enough contact. All groups supported more patient involvement in research; patients and advocates prioritized improvement in diagnosis and HCPs focused on clinical trials. This survey revealed significant unmet needs but differing perceptions regarding these among the groups. There is a need for investigation and collaboration to improve standards of care for NET patients.     

Serum and bronchial aspiration fluid HE-4 levels in lung cancer

Human epididymis 4 (HE-4) protein has been proposed as a tumor marker for lung and ovarian cancer. This study was designed to measure HE-4 levels in bronchial aspiration fluid (BAF) of patients with lung cancer and to describe the relationship of BAF HE-4 with known systemic increase in serum HE-4 levels. Sixty-four patients with lung cancer, 38 with benign lung disease and 19 healthy subjects, were enrolled in our study. The BAF was obtained during routine bronchoscopic procedure in patient groups. HE-4 levels in serum and BAF were measured with the commercially available kit by an enzyme-linked immunosorbent assay. Serum HE-4 levels were significantly higher in patients with lung cancer group (204.2?±?22.9 pmol/L) than in benign lung disease group (135?±?26.9 pmol/L, p?=?0.001) and healthy subjects (14.8?±?7.0 pmol/L, p?p?p?=?0.001) and age (p?相似文献   

Prevalence and impact of correlative science in breast cancer phase II trials

Correlative science (CS) can potentially augment clinical trial results by identifying biomarkers of response and resistance to a novel intervention. We evaluated recently published breast cancer phase II trials (BP2T) to determine prevalence, characteristics, and outcomes of CS. Through Pubmed, we identified BP2T of systemic therapy published between June 2005 and June 2010. A study-specific abstraction tool recorded trial characteristics, CS endpoints, source of tissue, adequacy of samples, biopsy safety, and CS outcomes. BP2T authors were contacted to verify abstraction results. Results were abstracted from 298 eligible trials enrolling 18,782 patients, of which 81 (27.2 %) involved CS. Of these, 57 (70.4 %) included tissue with 16 (28 %) using optional research biopsies and 17 (30 %) requiring mandatory research biopsies. No trial addressed biopsy safety issues. Trials were more likely to include CS if they were: industry versus non-industry sponsored (33.7 % vs. 17.1 %, p = 0.0017), neoadjuvant versus metastatic setting (47 % vs. 21.2 %, p = 0.0001), or U.S. versus non-U.S. trials (37 % vs. 21 %, p = 0.005). A minority of phase II breast cancer trials include CS representing a missed opportunity to learn more from clinical research. When CS is included, consistent reporting of endpoints, feasibility, outcomes, and safety is needed.     

Impact of Interactions Between Self-Reported Psychological Stress and Habitual Exercise on the Dietary Intake of Japanese Men and Women: a Large-Scale Cross-Sectional Study

Background: Modifying lifestyle factors such as diet and exercise can reduce the risk of cancer. Psychological stress (PS) might be indirectly associated with cancer because it alters lifestyle factors. However, the relationship among these variables has not been fully investigated. Thus, we examined interactions between self-reported PS (SRPS) and habitual exercise on diet. Materials and Methods: In all, 5,587 men and 2,718 women were divided into "exerciser" and "non-exerciser" groups, based on whether they exercised regularly, and classified into three SRPS levels: low, moderate and high. Diet was estimated using a validated food frequency questionnaire. Using a general linear model, food and nutrient consumption was estimated for each SRPS level in the 2 exercise groups, and the interactions between SRPS levels and exercise were calculated. Results: In women, the intake of pork and beef, low fat milk and yogurt, natto (fermented soybean), carrots and squash, other root vegetables, mushrooms, seaweeds, and wine, along with the nutrients vegetable protein, soluble, insoluble and total dietary fiber, daidzein, genistein, carotene, retinol equivalents, vitamin B2, pantothenic acid, potassium, calcium, magnesium, phosphorus and iron demonstrated significant interaction with SRPS and habitual exercise (p for interaction <0.05). In men, raw and green leafy vegetables and fruit and vegetable juice significantly interacted with SRPS and habitual exercise (p for interaction <0.05). Conclusions: We suggest that certain foods and nutrients, which are thought to have a protective effect against cancer, interact with SRPS and habitual exercise, especially in women. This information is valuable for understanding and improving interventions for cancer prevention.     

Laser flow cytometric studies on the intracellular accumulation of anthracyclines when combined with heat

The effects of heat on intracellular accumulation of anthracyclines were investigated by laser flow cytometry analysis. Sarcoma-180 cells were exposed to Adriamycin (ADM), epirubicin (EPIR), daunomycin (DM), THP-Adriamycin (THP), ME-2303 (ME) and KRN-8602 (KRN) at 37°C and at higher temperatures. There was a dose-dependent increase in the fluorescence intensity of all drugs at 37°C, but heat varied the fluorescence intensity of each drug. At 43°C the cellular fluorescence of ADM and EPIR increased by approximately 200%, but for DM the increase was 110–130%. The cellular fluorescence of THP and ME was little affected by heat, and heat reduced that of KRN to 80–90%. Each drug showed was unique in the relationship between drug exposure time and the fluorescence intensity at 37°C and 43°C. Cytotoxicity determined by the MTT assay was enhanced with heat in the cases of ADM and EPIR, but not with DM, THP, ME, or KRN. Thus, ADM and EPIR are expected to show enhanced antitumor activities when given in combination with hyperthermia.     

Factors affecting treatment choices in paediatric palliative care: comparing parents and health professionals

Study aim

When children with cancer are no longer curable, parents often need to decide between further aggressive treatments or symptom relief alone. Objectives were to: (1) Describe and compare factors influencing parent and healthcare professional (HCP) decision-making regarding the choice between chemotherapy versus supportive care alone in paediatric palliative care; and (2) Describe how these factors influence this choice.

Methods

Participants included parents of children with cancer without a reasonable chance of cure and health care professionals in paediatric oncology. Respondents were asked to indicate the preferred option and to report what factors affected their choice. Each factor was then rated on an importance visual analogue scale (VAS) ranging from 0 to 10. The importance scales were compared between parents and HCPs and the influence of importance ratings on preferred option was examined.

Results

A total of 77 parents and 128 health care professionals participated. For parents the median importance scores for hope, increased survival time and child quality of life were rated as most important (VAS score = 10). Parents rated these factors to be significantly more important than HCPs. Conversely, HCPs rated financial considerations more important than parents. For HCPs, stronger importance ranking for parent opinion was associated with stronger preference for aggressive chemotherapy.

Conclusion

Hope, increased survival time and child quality of life are all more important factors to parents when decision-making at end-of-life compared to HCPs. Conversely, HCPs place greater emphasis on the families’ financial considerations than parents. Understanding these differences may aid in communication and improve end-of-life care for children with cancer.     

Comparison of Diagnostic Accuracies of Serum HE-4 Levels and 3D Power Doppler Angiography Parameters between Benign Endometrial Pathologies and Endometrial Cancer

Purpose: To study the diagnostic accuracies of serum human epididymis protein 4 (HE-4) levels, virtual organ computer-aided analysis (VOCAL) parameters and endometrial volume in endometrial cancer cases. Materials and Methods: One hundred and seven patients (37 with endometrial cancer and 70 with benign endometrial pathology) were included in this study. VOCAL parameters and serum HE-4 levels were compared between the groups. Results: Area under the curve (AUC) values were 0.702, 0.658, 0.706 for vascularization index (VI), the flow index (FI) and the vascularization flow index (VFI), respectively. A cut off value of 0.568 for VI demonstrated 70% sensitivity, 72% specificity, 56% positive predictive value (PPV) and a81% negative predictive value (NPV). A cut off value of 25.8 for showed a senitivith of 70% and a specificity of 58% with aPPV of 46% and NPV of 78%, and with a cut off value of 0.12 for VFI 70%, 69%, 54% and 81%, respectively. The area under the curve for HE-4 was 0.814. A cut off value of 458 pmol/L was predictive of malignancy with 86% sensitivity and 63% specificity. Conclusions: VOCAL parameters and serum HE-4 levels were statistically significantly higher in the endometrial cancer patients. Serum HE-4 levels provided a greater sensitivity compared to power doppler angiography for predicting malignancy or benign endometrial pathology.     

Ondansetron (OND) vs granisetron (GRA) in the control of chemotherapy induced acute emesis

We enrolled 118 chemonaive cancer patients (pts) to receive OND i.v. dl or GRA i.v. dl. Seventy of the 118 pts received moderately emetogenic (ME) chemotherapy (140 cycles), while 48 received highly emetogenic (HE) chemotherapy (93 cycles). Therapeutic success was obtained in 89% (OND) vs 94% (GRA) cycles of HE and in 96.8% (OND) vs 95.6% (GRA) cycles of ME. The main toxicities were headache (24%, OND; 23%, GRA); light-headedness (13%, OND; 18%, GRA); constipation (11%, OND; 6%, GRA). In conclusion, we think that OND and GRA are effective and the two drugs are equally active and toxic.     

Talking about fertility in the context of cancer: health care professional perspectives

Health care professionals (HCPs) play a key role in providing information and counselling about the implications of cancer for fertility, however, many patients do not receive such information. The aim of this study was to examine the perspectives and practices of Australian HCPs in relation to discussing fertility with cancer patients. A mixed‐methods design, comprising of an online survey of 263 HCPs [41.4% nurses; 25.5% doctors; 31% allied health care professionals (AHP)] and qualitative interviews with 49 HCPs, was utilised. HCPs reported that fertility is an important concern for patients and their partners; however, only 50% of doctors and nurses, and 24% of AHPs reported that they always addressed this issue. The primary barriers to discussing fertility were poor patient prognosis; patient gender or age; time constraints; and absence of appropriate resources and materials. Only a minority of HCPs (29%) had undergone training in discussing fertility with cancer patients. The majority wanted further training or education: including nurses (81.8%), AHPs (80.6%) and doctors (55.4%). HCPs agreed that a number of resources would assist them to raise fertility with their patients, including a list of appropriate referral sources, fact sheets, information booklets, a fertility consultation checklist and on‐line resources.     

SARS-CoV-2 Infection and Antibody Seroprevalence among UK Healthcare Professionals Working with Cancer Patients during the First Wave of the COVID-19 Pandemic

AimsThe proportion of UK oncology healthcare professionals (HCPs) infected with SARS-CoV-2 during the COVID-19 pandemic's first wave is unknown. The primary aim of this study was to determine the SARS-CoV-2 infection and seroprevalence rates among HCPs.Materials and methodsPatient-facing oncology HCPs working at three large UK hospitals during the COVID-19 pandemic's first wave underwent polymerase chain reaction (PCR) and antibody testing [Luminex and point-of-care (POC) tests] on two occasions 28 days apart (June–July 2020).ResultsIn total, 434 HCPs were recruited: nurses (58.3%), doctors (21.2%), radiographers (10.4%), administrators (10.1%); 26.3% reported prior symptoms suggestive of SARS-CoV-2. All participants were PCR negative during the study, but 18.4% were Luminex seropositive on day 1, of whom 42.5% were POC seropositive. Nurses had the highest seropositive prevalence trend (21.3%, P = 0.2). Thirty-eight per cent of seropositive HCPs reported previous SARS-CoV-2 symptoms: 1.9 times higher odds than seronegative HCPs (P = 0.01). Of 400 participants retested on day 28, 13.3% were Luminex seropositive (92.5% previously, 7.5% newly). Thirty-two per cent of initially seropositive HCPs were seronegative on day 28.ConclusionIn this large cohort of PCR-negative patient-facing oncology HCPs, almost one in five were SARS-CoV-2 antibody positive at the start of the pandemic's first wave. Our findings that one in three seropositive HCPs retested 28 days later became seronegative support regular SARS-CoV-2 PCR and antibody testing until widespread immunity is achieved by effective vaccination.     

Enhanced apoptosis and radiosensitization by combined 13-cis-retinoic acid and interferon-alpha2a; role of RAR-beta gene.

PURPOSE: Combined use of 13-cis-retinoic acid (cRA) and interferon-alpha2a (IFNalpha) induced significant radiosensitization in human cervical cancer ME-180 cell line, whereas it failed to achieve similar radiation enhancement in HeLa cells. The differential radiosensitization could be from the difference of retinoic acid receptor (RAR) expression because RAR-beta was highly expressed in ME-180 cells in contrast to the HeLa cells where RAR-beta was not detectable. We examined the role of this gene in mediating radiosensitization by cRA and IFNalpha, and explored the mechanism of radiation-induced cell killing. METHODS AND MATERIALS: Human cervical cancer cell lines, ME-180 and HeLa, were treated with cRA and IFNalpha followed by radiation. Apoptosis and radiosensitization were quantitated by TUNEL assay (in situ DNA nick end labeling) and colony-forming ability of surviving cells. The cells were transfected with bcl-2 gene and RAR-beta gene to test the role of these genes in mediating radiosensitization and apoptosis. RESULTS: Synergistic radiosensitization and apoptosis was observed by combined use of cRA and IFNalpha with radiation in ME-180 cells which express high level of RAR-beta mRNA, whereas these were not seen in HeLa cells where RAR-beta mRNA is not detectable. Both radiosensitization and apoptosis were abolished by bcl-2 gene in ME-180 cells. RAR-beta gene transfection induced similar radiation enhancement and apoptosis in HeLa cells. CONCLUSION: Apoptosis and radiation response were enhanced in the cells with high level of RAR-beta mRNA expression. The RAR-beta gene appears to mediate the radiation-induced apoptosis by cRA and IFNalpha. These findings indicate that presence of RAR-beta in the cancer cells could be exploited for patient selection in using these drugs for apoptosis and radiosensitization.     

Perceived importance of emotional support provided by health care professionals and social networks: Should we broaden our focus for the delivery of supportive care?

Introduction

Emotional support provided by health care professionals (HCPs) for people diagnosed with cancer is associated with improved outcomes. Support via social networks may also be important.

Aims

To report among a sample of distressed patients and caregivers, (1) the importance attributed to different sources of emotional support (HCPs and social networks) by distressed cancer patients and caregivers; (2) the proportion who indicate they did not receive sufficient levels of emotional support; and (3) potential associations between respondents’ demographic and clinical characteristics and reported lack of emotional support.

Methods

This study utilised cross-sectional data from telephone interviews collected during the usual-care phase of the Structured Triage and Referral by Telephone (START) trial. Participants completed a telephone interview 6 months after their initial call to the Cancer Council Information and Support service and included recall of importance and sufficiency of emotional support.

Results

More than two-thirds of patients (n = 234) and caregivers (n = 152) reported that family and friends were very important sources of emotional support. Nurses (69% and 42%) and doctors (68% and 47%) were reported very important, while a lower proportion reported that psychologists and psychiatrists were very important (39%, and 43%). Insufficient levels of support were reported by 36% of participants. Perceptions of insufficient support were significantly associated with distress levels (p < .0001) and not having a partner (p = .0115).

Conclusion

Social networks, particularly family, are an important source of emotional support. Higher levels of distress, those without partners, and caregivers may require targeted interventions to increase their access to emotional support.     

In vitro radiosensitization of human cervical carcinoma cells by combined use of 13-cis-retinoic acid and interferon-α2a

Background: Significant antitumor activity has been reported with the combined use of 13-cis-retinoic acid (cRA) and interferon-α2a (IFN-α) in the treatment of advanced-stage cervical cancers and skin cancers. Since IFN-α has been shown to be a modest radiation enhancer for selected malignant tumor cells and the cytotoxic activity is more enhanced by combining cRA and IFN-α, we hypothesized that the exposure of selected human carcinoma cells to combined cRA and IFN-α would render the cells highly radiosensitive.Methods and Materials: Two human cervical carcinoma cell lines, ME-180 and HeLa-S3, were chosen for the present study because of the different characteristics of the retinoic acid receptor status of the cell lines. To demonstrate the effects of combined cRA and IFN-α treatment on radiation response, we exposed the cells to cRA, IFN-α, or a combination of the drugs for 72 h before radiation. Experiments were carried out at minimally cytotoxic concentrations of the drug for radiation studies. End points of the study were cell growth inhibition and clonogenic ability of the single-plated cells. Effects of cRA and IFN-α on radiation response were quantitatively analyzed by constructing the radiation cell survival curves of ME-180 and HeLa cells.Results: ME-180 cells exhibited varying degrees of cytotoxicity with cRA and IFN-α, while HeLa cells showed no toxic effects with the same treatment. Combined treatment of cRA and IFN-α produced an additive cytotoxic effect in ME-180 cells. Radiosensitization was minimal when ME-180 cells were treated with either cRA or IFN-α before radiation. When ME-180 cells were exposed to 10 μM cRA for 48 h and 1000 U/ml IFN-α for 24 h prior to radiation, there was a significant enhancement in radiation-induced cell killing; the dose modification factor was 2.1 ± 0.9 at the 1% cell-survival level. On the other hand, HeLa-S3 cells exhibited no increased cytotoxicity or radiation enhancement under the same experimental conditions.Conclusion: The present data provide a radiobiological basis for using cRA and IFN-α as a combination radiosensitizer in selected human carcinoma cells.